scholarly journals Effect of Poly(I:C) and melanoma B16-F10 on the immunophenotype of murine spleen cells

2021 ◽  
Vol 20 (4) ◽  
pp. 51-58
Author(s):  
A. V. Ponomarev ◽  
A. A. Rudakova ◽  
Z. A. Sokolova ◽  
M. A. Baryshnikova ◽  
V. S. Kosorukov
Keyword(s):  
T Cells ◽  
Nk Cells ◽  
Repeated Administration ◽  
Poly I:C ◽  
Control Group ◽  
Spleen Cells ◽  
Murine Splenocytes ◽  
Melanoma B16 ◽  
Murine Spleen ◽  
Tumor Load

Introduction. It is known that the agonist of TLR-3 Poly(I:C), used as an adjuvant in a number of models of antitumor vaccines, causes inhibition of melanoma B16 growth, but the immunological aspects involved in this process have not been fully studied.The aim of the study was to evaluate changes of the immunophenotype of the spleen cells of C57BL / 6 mice caused by the tumor load and / or Poly(I:C), which is necessary for better understanding of the processes occurring during Poly(I:C) inhibition of melanoma B16-F10.Materials and methods. The immunophenotype of splenocytes of C57Bl / 6 mice was studied by flow cytometry asfollowing: the group 1 was a control (intact animals), the group 2 was mice with subcutaneously transplanted melanoma B16-F10, the group 3 was mice without a tumor treated with Poly(I:C) and the group 4 – mice with subcutaneously transplanted melanoma B16-F10 treated with Poly(I:C).Results. Median values of parameters such as the CD4 / CD8 immunoregulatory index, the percentage of CD69+ CD4+ and CD8+ T cells, the number of B and NK cells for the group of mice with melanoma treated with Poly(I:C) were between the values in the control group and in the group of mice with B16-F10. when comparing the results, the number of B and NK cells, the percentage of CD69+ on CD4+ and CD8+ T cells, their median in the group of mice with melanoma treated with Poly(I:C) was closer to the control than to the values obtained in the B16-F10 group and in the group of healthy mice receiving Poly(I:C). At the same time, we found that the total number of CD3+ cells, the number of naive CD4+ and CD8+ T cells was higher in the group of mice with melanoma treated with Poly(I:C) compared to all other groups.Conclusion. The analysis revealed the changes of the immunophenotype of murine spleen cells (CD4 / CD8, the percentage of CD69+ CD4+ and CD8+ T cells, the number of B and NK cells), which were affected by the tumor load and / or the administration of Poly adjuvant (I:C). Changes in the immunophenotype of murine splenocytes were associated with the tumor load and its size. It was also found that the splenocyte immunophenotype was affected by the repeated administration of Poly(I:C) during the tumor growth.

scholarly journals Tumor necrosis serum induces a serologically distinct population of NK cells.

1979 ◽  
Vol 150 (3) ◽  
pp. 426-431 ◽  
Author(s):  
M Chun ◽  
V Pasanen ◽  
U Hämmerling ◽  
G F Hämmerling ◽  
M K Hoffmann
Keyword(s):  
T Cells ◽  
Nk Cells ◽  
Tumor Necrosis ◽  
Nk Cell ◽  
Chromosome 17 ◽  
Cell Type ◽  
Spleen Cells ◽  
Distinct Population ◽  
Thymic Function ◽  
Murine Spleen

Murine spleen cells generate nonspecific cytotoxic cells, referred to as natural killer (NK) cells, within 4 d of incubation in Mishell-Dutton cultures. This NK cell type does not arise in cultures of BALB/c.nu spleen cells or in cultures of T-cell depleted C57BL/6 spleen cells, indicating that its activation depends on T cells. Another type of NK cells is induced by tumor necrosis serum in murine spleen-cell cultures. It arises within 24 h and its activation does not depend on T cells. This cell type (and its precursor) expresses the recently discovered cell-surface marker Qa5 (controlled by the Q region of chromosome 17) that distinguishes this NK cell from the NK cell that depends for its activation on thymic function. Qa5+ NK cells are also induced by interferon.

Immune-metabolome response to an acute exercise exertion reveals dysfunctional metabolic recovery in heart failure

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
N Kraenkel ◽  
A Koc ◽  
S Kaczmarek ◽  
K Lehnert ◽  
I Urbaneck ◽  
...  
Keyword(s):  
Heart Failure ◽  
T Cells ◽  
Cardiovascular Risk ◽  
Nk Cells ◽  
Cardiopulmonary Exercise Testing ◽  
Risk Profile ◽  
Left Ventricular ◽  
Metabolic Parameters ◽  
Control Group ◽  
Cardiovascular Risk Profile

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): BMBF Background Patients with heart failure with reduced ejection fraction (HFrEF) have an increased inflammatory load and impaired cardiac oxidative lipid phosphorylation. Early dysregulations of pathophysiological alterations may not be detectable if patients are assessed under resting conditions. Purpose We exposed HFrEF patients to a physical exertion challenge by cardiopulmonary exercise testing (CPET) and determined inflammatory and metabolic parameters before, during and 2 hours after the test. Methods A symptom-limited CPET was performed in participants with HFrEF (n = 16) and age and sex matched controls (CON, n = 13). In addition to clinical and physiological parameters, we assessed blood counts of leukocyte subtypes, their morphology, aggregation with platelets and microvesicle release, as well as plasma cytokines and metabolites at baseline (T1), immediately after CPET (T2), and after 2 hours of rest (T3). Inflammatory and metabolic parameters were measured using the ThermoFischer ProcartaPlex Human Inflammation-Panel and Biocrates MxP® Quant 500 kit, respectively. Non-parametric tests were chosen and all multiple tests were adjusted by the Benjamini-Hochberg method. Results Cardiovascular risk profile of HFrEF and CON was similar. In agreement with the definition for HFrEF, these patients had a lower EF and a greater left ventricular enddiastolic diameter compared to CON. There were no differences between groups for leukocyte, cytokine or metabolic parameters at T1. Immediately after CPET, 20 parameters were significantly increased in both groups, including an increase of lactate, natural killer (NK) and NK T cell blood counts. In addition, 131 inflammatory and metabolic parameters were upregulated only in HFrEF, as compared to only 17 in CON. In HFrEF-platelet aggregates with NK cells, CD8+ cytotoxic T cells and "classical" CD14++CD16-monocytes, 58 different phosphatidylcholines and 21 triglycerides were upregulated immediately after exercise. At T3 almost all altered parameters returned to baseline in CON while in HFrEF blood counts and morphological markers of inflammatory effector cell types, including NK cells, CD8+ T cells and neutrophils, as well as genomic nuclear DNA, an indicator of cell death, remained elevated. Moreover, several triglycerides did not return to baseline in HFrEF after a 2-hour resting period. In these patients, but not in CON, the different lipids (i.e. phosphatidylcholine, triglycerides) strongly correlated with pro-inflammatory cytokines and NK cells. Conclusion Our data support the concept of impaired fatty acid utilization and inflammation-mediated metabolic dysregulation in HFrEF. However, the correlations between metabolic and inflammatory parameters were not detected at baseline in comparison to a control group with similar cardiovascular risk profile. Therefore, investigating patients in response to a physical or metabolic challenge might reveal early pathological changes.

IMMU-44. AN IMMUNOTHERAPEUTIC VACCINE COMPOSED OF IRRADIATED WHOLE TUMOR CELLS PULSED WITH MANNAN-BAM, TLR LIGANDS AND ANTI-CD40 ANTIBODY INDUCES POTENT IMMUNE RESPONSE IN PRECLINICAL GBM ANIMAL MODEL

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi102-vi102
Author(s):  
Herui Wang ◽  
Rogelio Medina ◽  
Juan Ye ◽  
Pashayar Lookian ◽  
Ondrej Uher ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Tumor Cells ◽  
T Lymphocyte ◽  
Cd8 T Cells ◽  
Therapeutic Efficacy ◽  
Poly I:C ◽  
Control Group ◽  
Complete Regression ◽  
Adaptive Immune

Abstract Despite numerous therapeutic advances, the treatment of glioblastoma multiforme (GBM) remains a challenge, with current 5-year survival rates estimated at 4%. Multiple characteristic elements of GBM contribute to its treatment-resistance, including its low immunogenicity and its highly immunosuppressive microenvironment that can effectively disarm adaptive immune responses. Hence, therapeutic strategies that aim to boost T-lymphocyte mediated responses against GBM are of great therapeutic value. Herein, we present a therapeutic vaccination strategy that promotes the phagocytosis of tumor cells, enhances tumor antigen presentation, and induces a tumor-specific adaptive immune response. This strategy consists of vaccinations with irradiated whole tumor cells (rWTC) pulsed with phagocytic agonists (Mannan-BAM), TLR ligands [LTA, Poly (I:C), and R-848], and anti-CD40 antibody (collectively abbreviated as rWTC-MBTA). We evaluated the therapeutic efficacy of rWTC-MBTA strategy in a mouse syngeneic GL261 orthotopic GBM tumor model. rWTC-MBTA or vehicle control were administered subcutaneously over the right foreleg three days after intracranial injection of GL261 cells. Complete regression (CR) of intracranial tumors was achieved in 70% (7/10) of rWTC-MBTA treated animals while none survived in the control group. Immunophenotyping analyses of peripheral lymph nodes and brain tumors of rWTC-MBTA treated mice demonstrated: (1) increased mature dendritic cells and MHC II+ monocytes; (2) increased effector (CD62L-CD44+) CD4-T and CD8-T cells; (3) increased cytotoxic IFNγ-, TNFα-, and granzyme B-secreting CD4-T and CD8-T cells. Of note, the therapeutic efficacy of rWTC-MBTA disappeared in CD4-T and/or CD8-T lymphocyte depleted mice. Three mice that achieved CR were rechallenged with 50k GL261 cells intracranially 14 months after the last rWTC-MBTA treatment and all rechallenged animals resisted GL261 tumor development, confirming the establishment of long-term immunological memory against GL261 tumor cells. Collectively, our study demonstrated that rWTC-MBTA strategy can effectively activate antigen presenting cells and induce more favorable T-cell signatures in the GBM tumors.

Determination of Soluble MICA in Serum as a Novel Marker for Tumor Stage and Metastasis.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1344-1344
Author(s):  
Helmut R. Salih ◽  
Petra Stieber ◽  
Andrea Peterfi ◽  
Dorothea Nagel ◽  
Lothar Kanz ◽  
...  
Keyword(s):  
T Cells ◽  
Differential Diagnosis ◽  
Nk Cells ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Cd8 T Cells ◽  
Control Group ◽  
Healthy Individuals ◽  
Benign Disorders

Abstract The human NKG2D ligands (NKG2DL) MICA and MICB have been shown to be expressed on tumors of epithelial and hematopoietic origin in vivo. Recently we reported that MICA is shed from the cell surface of tumor cells and is present in sera of tumor patients (J Immunol169:4098 (2002), Blood102:1389 (2003)). Since the strength of an anti-tumor response by NK cells and CD8 T cells is critically depending on NKG2DL expression levels, down-regulation of MICA-expression on tumor cells represents an immune escape mechanism that diminishes anti-tumor reactivity of NKG2D-bearing lymphocytes. However, no data are yet available regarding the correlation of soluble MICA (sMICA) levels with specific tumor entities, aggressiveness of the disease, and hence the potential implementation of sMICA as novel marker in differential diagnosis and prognosis of cancer. In this study, we determined sMICA levels in sera of 512 individuals including 296 patients with various cancers, 154 patients with benign disorders and 62 healthy individuals. Healthy individuals revealed significantly lower sMICA values (median<30pg/mL) than patients with benign diseases (84pg/mL; p=0.005) and cancer patients (161pg/mL; p<0.0001). In addition, sMICA levels differed significantly between cancer patients and patients with benign disorders (p<0.0001) that represent the most relevant control group for differential diagnosis. In cancer patients, while there was no association between sMICA levels and tumor size (p=0.456), cell differentiation (p=0.271), or lymph node involvement (p=0.674), sMICA correlated significantly with cancer stage and metastasis (p=0.015 and p=0.007, respectively). Our data indicate that release of MICA might play a role in late stages of tumor progression by overcoming the confining effect of NK cells and CD8 T cells. Thus, determination of sMICA levels provides valuable information for cancer staging, and sMICA in serum seems to be an indicator for systemic manifestation of malignancy rather than for local tumor extent.

Improved Immune Recovery after Transplantation of TCRαβ/CD19 Depleted Allografts from Haploidentical Donors in Pediatric Patients

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 852-852
Author(s):  
Peter Lang ◽  
Tobias Feuchtinger ◽  
Heiko-Manuel Teltschik ◽  
Wolfgang Schwinger ◽  
Patrick Schlegel ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
T Lymphocytes ◽  
Nk Cells ◽  
Pediatric Patients ◽  
Conflicts Of Interest ◽  
Γδ T Cells ◽  
Control Group ◽  
Unrelated Donor ◽  
Immune Recovery

Abstract Transplantation of haploidentical stem cells has become an accepted option for pediatric patients and adults with high risk malignancies who lack a matched related or unrelated donor. In recent years, the majority of pediatric transplant centers chose the CD34 positive selection of peripheral stem cells, which allowed minimizing GvHD by effective reduction of T cells in the graft. However, infectious complications caused by delayed immune recovery were a major reason for transplant related mortality (TRM). In order to improve the immune recovery, we have established a new T-cell depletion method which removes αβ+ T-lymphocytes via a biotinylated anti-TcRαβ antibody followed by an anti-biotin antibody conjugated to magnetic microbeads while retaining γδ+ T-lymphocytes, natural killer (NK) cells and other cells in the graft. In addition, CD19+ B-lymphocytes were concomitantly depleted for the prevention of post-transplant EBV-associated lymphoproliferative disease. Immune recovery was retrospectively analyzed in a cohort of 41 patients with acute leukemia, MDS and non-malignant diseases, who received αβ T and B cell depleted allografts from haploidentical family donors. Conditioning regimens consisted of fludarabine or clofarabine, thiotepa, melphalan and serotherapy with OKT3 or ATG-Fresenius®. Graft manipulation was carried out with anti TCRαβ and anti CD19 antibodies and immunomagnetic microbeads. γδ T cells and NK cells remained in the grafts. Primary engraftment occurred in 88%, acute graft versus host disease (aGvHD) grade II and III-IV occurred in 10% and 15%. Immune recovery data were available in 26 patients and comparable after OKT3 (n=7) or ATG-F® (n=19). Median time to reach > 100 CD3+/µl, > 200 CD19+ cells/µl and > 200 CD56+ cells/µl for the whole group was 13, 127 and 12.5 days. Compared to a historical control group of patients with CD34 positive selected grafts, significantly higher cell numbers were found for CD3+ at days +30 and +90 (267 vs. 27 and 397 vs. 163 cells/µl), for CD3+4+ at day +30 (58 vs. 11 cells/µl) and for CD56+ at day +14 (622 vs. 27 cells/µl). The clinical impact of this accelerated immune recovery will be evaluated in an ongoing prospective multi-center trial. Disclosures No relevant conflicts of interest to declare.

scholarly journals Does massive  bowel resection in newborns  affect further  immunity in children ?

2020 ◽  
Author(s):  
Katarzyna Sznurkowska ◽  
Anna Borkowska ◽  
Agnieszka Jankowska ◽  
Magdalena Malanowska ◽  
Maciej Zagierski ◽  
...  
Keyword(s):  
T Cells ◽  
Nk Cells ◽  
Bowel Resection ◽  
Clinical Signs ◽  
Peripheral Lymphocyte ◽  
Control Group ◽  
Healthy Children ◽  
Activated T Cells ◽  
Serum Immunoglobulins ◽  
Lymphocyte Populations

Abstract Background Short bowel syndrome (SBS) is defined as the a malabsorptive condition most often caused by massive resection of the small intestine. In children most cases of SBS originate in the newborn period and result from congenital anomalies or necrotizing enterocolitis. Loss of gut mucosa during resection does not only mean loss of absorption surface, but also deprives organism of many immunocompetent cells concentrated in gut associated lymphoid tissue, which is regarded the largest immune organ in humans. Aim of the study: We have aimed to access the influence of bowel resection on adaptive immunity in children, basing on peripheral lymphocyte populations and serum immunoglobulins. Patients and methods: 18 children, who underwent bowel resection in the first month of life and required further home parenteral nutrition were enrolled into the study. 12 healthy children, constituted control group. Based on flow cytometry the following subpopulations of lymphocytes were evaluated: T, B, NK, CD4+, C8 + and activated T cells. Serum immunoglobulins were determined with the use of immunoturbidimetric method. Results The percentage of B lymphocytes was reduced, while the rates of lymphocytes T and CD8 + lymphocytes were higher compared to healthy children. We documented significantly lower absolute count and proportion of NK cells in SBS group than in the control group. Absolute counts of lymphocytes, lymphocytes B, T, CD4 + and percentages of lymphocytes CD4+, and activated T cells inversely correlated with the time after resection. No statistically significant differences were found between the levels of IgA, IgM and IgG in the studied and the control group Conclusions Children with SBS do not present with clinical signs of immunodeficiency as well as deficits in peripheral lymphocyte populations and serum immunoglobulins. Lower number of NK cells in SBS patients compared to healthy children needs to be verified in larger cohort. The tendency of the lymphocyte subpopulations to decrease over time after resection points out the necessity for longer follow- up.

scholarly journals "Anomalous" THY-1(+) killer cells in allogeneic and F1-anti-parental mixed leukocyte culture. Relation to natural killer cells and allospecific cytotoxic T lymphocytes

1982 ◽  
Vol 156 (2) ◽  
pp. 385-403 ◽  
Author(s):  
K Karre ◽  
JK Seeley ◽  
E Eriksson ◽  
RC Burton ◽  
R Kiessling
Keyword(s):  
T Cells ◽  
Nk Cells ◽  
Natural Killer ◽  
Mouse Serum ◽  
Blast Transformation ◽  
Spleen Cells ◽  
Killer Cells ◽  
Ctl Response ◽  
Leukocyte Culture ◽  
Antigenic Properties

Anomalous killer cells are Thy-1(+) blasts that are cytolytic to the natural killer (NK)-sensitive lymphoma YAC-1, and that can be detected early (day 3-4) in the period preceeding the allospecific cytotoxic T lymphocyte (CTL) response in (CBA x A)F1 {arrow} C57B1 mixed leukocyte culture (MLC). We have investigated the origin and nature of anomalous killing (AK), with special emphasis on its relation to NK-and allospecific CTL-activity. AK was shown to be distinct from the previously described "NK(c)-cells" induced by cultivation in fetal calf serum (FCS)-supplemented medium when these two reactivities were examined in parallel. AK was detected in either FCS- or normal mouse serum (NMS)-supplemented allogeneic MLC, indicating that the response was not dependent on mitogenic or antigenic properties of heterologous serum. In addition to several H-2-incompatible combinations, AK was also observed in an Mls-incompatible (but H-2 compatible) and two F(1)- antiparental MLC responder/stimulator combinations. AK cells showed a similar selectivity pattern to NK cells, as demonstrated in cold target inhibition and direct cytotoxicity assays using variant or interferon-modulated YAC-1 cells with low expression of NK target structures. The AK-cells were NK- 1.2(-/weak). Thy-l.2(+), although they seem to be derived from non-adherent radiosensitive cells which are closely related, if not identical, to NK-cells (NK-1.2(+). Thy-l.2(-/weak)), as they could not be readily induced in responder populations with low NK-activity but normal allospecific CTL potential. Conversely, an in vivo thymectomy protocol or treatment of normal spleen cells with monoclonal anti-Thy-1.2 + C reduced the allospecific CTL response drastically but did not affect the AK response. Anomalous killers were not observed when MLC were prepared with responder as well as stimulator cells devoid of mature T cells. In such a combination, the AK response could be partially restored by the addition of irradiated +/nu (but not nu/nu) responder cells to the cultures. When normal (non-nude) spleen cells were used as responders, induction of AK did not require the presence of T cells in the stimulator population, whereas the removal of adherent and phagocytic cells from stimulators abrogated the response. Taken together, the results suggest that AK represents activation, blast transformation, and surface marker modulation of NK cells induced by alloantigen-stimulated T cells, resulting in Thy-1(+) cytolytic cells with similar properties to those described for NK lines, Although AK cells may be regarded as a more T cell-like NK phenotype, their induction is neither necessary, nor sufficient for generation of specific CTL in MLC.

scholarly journals Heterogeneity of natural killer cells in the mouse.

1981 ◽  
Vol 154 (2) ◽  
pp. 306-317 ◽  
Author(s):  
J A Lust ◽  
V Kumar ◽  
R C Burton ◽  
S P Bartlett ◽  
M Bennett
Keyword(s):  
B Cells ◽  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Cell Activity ◽  
Spleen Cells ◽  
Murine Spleen ◽  
Total Body

Mice were treated with the bone-seeking isotope, 89Sr, cyclophosphamide, and short-term lethal irradiation in vivo, and murine spleen cells are treated with anti-Nk-1.2 plus complement (C) in vitro. Fresh spleen cell suspensions from the above groups and from beige and neonatal mice were subsequently tested for natural killer (NK) cell activity against a panel of lymphoid and nonlymphoid tumor cell target. NK cell reactivities against YAC-1, MPC-11, and Cl.18 tumors were markedly and consistently reduced in (a) mice treated with 89Sr, (b) spleen cells treated with anti-Nk-1.2 plus C, and (c) C57BL/6 bg/bg mice. In contrast, NK activities against FLD-3 and WEHI-164.1 tumors were usually normal in mice treated with 89Sr, in beige mutant mice, and in spleen cells after treatment with anti-Nk-1.2 antibody and C. It appears, therefore, that two major groups of NK cells exist in fresh mouse spleen cells suspensions. NK-A cells are marrow dependent, Nk antigen positive, and deficient in beige mice; these lyse YAC-1, MPC-11, and Cl.18 tumors. NK-B cells, which are responsible for the lysis of WEHI-164.1 and FLD-3, are Nk antigen negative, marrow independent, and unaffected by the bg/bg mutation. Other features of NK-B cells, suggest that these NK cells, although they share the characteristics mentioned above, differ among themselves especially with respect to age of maturation and susceptibility to cyclophosphamide and total body irradiation. The NK-B group may therefore induce subsets that remain to be defined.

scholarly journals Decidual immune response following COVID-19 during pregnancy varies by timing of maternal SARS-CoV-2 infection

2021 ◽  
Author(s):  
Lillian J Juttukonda ◽  
Elisha M Wachman ◽  
Jeffery Boateng ◽  
Mayuri Jain ◽  
Yoel Benarroch ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune Responses ◽  
Nk Cells ◽  
Control Group ◽  
Decidua Basalis ◽  
Tnf Α ◽  
Show Evidence ◽  
Negative Controls ◽  
In Pregnancy

While COVID-19 infection during pregnancy is common, fetal transmission is rare, suggesting that intrauterine mechanisms form an effective blockade against SARS-CoV-2. Key among these is the decidual immune environment of the placenta. We hypothesized that decidual leukocytes are altered by maternal SARS-CoV-2 infection in pregnancy and that this decidual immune resonse is shaped by the timing of infection during gestation. To address this hypothesis, we collected decidua basalis tissues at delivery from women with symptomatic COVID-19 during second (2nd Tri COVID, n=8) or third trimester (3rd Tri COVID, n=8) and SARS-CoV-2-negative controls (Control, n=8). Decidual natural killer (NK) cells, macrophages and T cells were evaluated using quantitative microscopy, and pro- and anti-inflammatory cytokine mRNA expression was evaluated using quantitative reverse transcriptase PCR (qRT-PCR). When compared with the Control group, decidual tissues from 3rd Tri COVID exhibited significantly increased macrophages, NK cells and T cells, whereas 2nd Tri COVID only had significantly increased T cells. In evaluating decidual cytokine expression, we noted that IL-6, IL-8, IL-10 and TNF-α were significantly correlated with macrophage cell abundance. However, in 2nd Tri COVID tissues, there was significant downregulation of IL-6, IL-8, IL-10, and TNF-α. Taken together, these results suggest innate and adaptive immune responses are present at the maternal-fetal interface in maternal SARS-CoV-2 infections late in pregnancy, and that infections earlier in pregnancy show evidence of a resolving immune response. Further studies are warranted to characterize the full scope of intrauterine immune responses in pregnancies affected by maternal COVID-19.

Cytotoxic cells induced during lymphocytic choriomeningitis virus infection of mice: natural killer cell activity in cultured spleen leukocytes concomitant with T-cell-dependent immune interferon production

1980 ◽  
Vol 30 (2) ◽  
pp. 473-483
Author(s):  
R M Welsh ◽  
W F Doe
Keyword(s):  
T Cells ◽  
T Cell ◽  
Nk Cells ◽  
Nk Cell ◽  
Cytotoxic T Cells ◽  
Cell Activity ◽  
Lymphocytic Choriomeningitis ◽  
Type I ◽  
Spleen Cells

The characteristics and specificities of spleen and peritoneal cytotoxic cells generated during lymphocytic choriomeningitis virus (LCMV) infection of C3H/St mice were examined. Activated natural killer (NK) cell activity was identified in fresh leukocyte populations from the 2nd to 8th days postinfection, whereas virus-specific cytotoxic T-cell activity was detected from the 6th to 14th days. When leukocytes were cultured overnight at 37 degrees C before assay, T-cell activity was still observed, but nonspecific activated NK cell-like cytotoxicity was only detected on the 6th and to a lesser degree the 8th day postinfection. Overnight culture of leukocytes taken earlier in the infection eliminated their NK cell activity. Similar activities were seen with spleen cell, plastic-adherent peritoneal cell, and nonadherent peritoneal cell populations. The virus-specific cytotoxicity observed with adherent peritoneal cells was due to contamination with cytotoxic T cells, as shown by H-2-restricted cytotoxicity and sensitivity to anti-theta antibody and complement. The nonspecific cultured day 6 effector cell from either the spleen or peritoneum displayed killing specificities and other physical properties identical to those of activated NK cells, but had sensitivities to anti-theta antibody and complement intermediate between activated day 3 NK cells and cytotoxic T cells. Culture stable NK-like cells were not found in athymic nude mice, suggesting a T-cell-dependent mechanism. Whereas LCMV spleen homogenates contained 10-fold-higher levels of interferon at day 2 than at day 6 postinfection, substantially more (nearly 20-fold) interferon was made in cultures of day 6 cells than day 2 cells. Spleen interferon was predominantly type I, whereas the culture interferon was predominantly type II, as shown by acid lability studies. Significant levels of interferon were produced by nylon-wool-passed day 6 spleen cells, and virtually all interferon production was eliminated by treatment of either day 2 or day 6 cells with antibody to theta antigen and complement, suggesting that T cells produced the interferon in vitro. Furthermore, athymic nude mice had no culture-stable NK cells 6 days postinfection, and spleen cells from them failed to produce significant levels of interferon in vitro. Addition of interferon (type I, fibroblast) to cultured C3H spleen cells affect the already elevated levels of cytotoxicity in day 6 cultures, suggesting that the NK cells in the day 6 culture were already activated. Our results suggest that T cells responding to LCMV infection secrete interferon type II which causes the continued activation of NK cells in culture. The resulting population of activated NK cells therefore appears to be relatively stable in culture and to express more theta antigen because of this T-cell dependence. Although one could mistakenly or allospecific cytotoxic T cells or cytotoxic macrophages, more careful examination shows that they are most likely activated NK cells...

Sign in / Sign up

Export Citation Format

Share Document