scholarly journals Different Cytokine Production and Effector/Memory Dynamics of αβ+ or γδ+ T-Cell Subsets in the Peripheral Blood of Patients with Active Pulmonary Tuberculosis

2003 ◽  
Vol 16 (3) ◽  
pp. 247-252 ◽  
Author(s):  
C. Gioia ◽  
C. Agrati ◽  
D. Goletti ◽  
D. Vincenti ◽  
S. Carrara ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
Pulmonary Tuberculosis ◽  
Peripheral Blood ◽  
Cell Subset ◽  
T Cell Response ◽  
T Cell Subsets ◽  
Effector Memory ◽  
Cell Dynamics ◽  
Active Pulmonary Tuberculosis

Immunity to M.tuberculosis (MTB) infection consists of interactions between various T-cell subsets that control the infection and prevent further reactivation. We analysed the effector/memory T-cell dynamics and cytokines production in the peripheral blood of patients with pulmonary tuberculosis (TB). We observed that the frequency of CD4+ T-cell effectors was significantly increased during active TB, confirming a major role of this T-cell subset in TB immunity. Pre-terminally differentiated CD8+ T-lymphocytes were increased in the peripheral blood as well. In contrast, we observed a reduced number of effector mycobacteria-reactive γδ+ T-lymphocytes with a specific defects in reacting to mycobacterial nonpeptidic antigens, suggesting that this innate response is rapidly lost during TB infection. Nevertheless, the frequency of γδ+ T-cells effectors in TB patients was higher than the αβ+ T-cell response to peptide from MTB-ESAT-6 protein and quantitatively similar to PPD reactivity. Thus, αβ+and γδ+ T-cell differentiation and function are differently triggered by active TB infection.

scholarly journals Analysis of Peripheral Inflammatory T Cell Subsets and Their Effector Function in Patients With Birdshot Retinochoroiditis

2020 ◽  
Author(s):  
Janine Trombke ◽  
Lucie Loyal ◽  
Braun Julian ◽  
Pleyer Uwe ◽  
Thiel Andreas ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Peripheral Blood ◽  
Cell Subset ◽  
Disease Status ◽  
Effector Function ◽  
T Cell Subsets ◽  
Effector Memory ◽  
Main Site ◽  
Birdshot Retinochoroiditis

Abstract Purpose: Birdshot Retinochoroiditis (BSRC) is a progressive non-infectious intraocular inflammation that affects choroid and retina. Inflammatory processes have adverse effects on vision by affecting photoreceptor-bearing cells that do not regenerate. Methods: This study aimed at characterizing inflammatory CD4+ and CD8+ T cell subsets in the peripheral blood of BSRCs. Furthermore, we correlated phenotypical and functional immunological analyses with clinical data. Results: We observed a slight increase of terminally differentiated effector memory CD8+ T cells expressing CD45RA (TEMRA) in blood of inactive, compared to active BSRCs. Moreover, we identified a trend for a decreased population of TH2 cells and increased TH1 frequencies in active BSRCs, a typical sign of ongoing autoimmune processes. Functional assays demonstrated severe and overall impairment of effector function of both, CD4+ and CD8+ inflammatory T cells, which might reflect T cell exhaustion. Conclusion: Although the eye is the main site of inflammation in BSRC, we observed altered T cell subset compositions in the peripheral blood, dependent on the disease status. Our results indicate that T cells may play a major role in BSRC pathology, although our cohort size is too limited for definitve conclusions. Future studies with larger and well-defined cohorts of BSRCs have to be performed.

scholarly journals Analysis of peripheral inflammatory T cell subsets and their effector function in patients with Birdshot Retinochoroiditis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Janine Trombke ◽  
Lucie Loyal ◽  
Julian Braun ◽  
Uwe Pleyer ◽  
Andreas Thiel ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Peripheral Blood ◽  
Cell Subset ◽  
Disease Status ◽  
Effector Function ◽  
T Cell Subsets ◽  
Effector Memory ◽  
Main Site ◽  
Birdshot Retinochoroiditis

AbstractBirdshot Retinochoroiditis (BSRC) is a progressive non-infectious intraocular inflammation that affects choroid and retina. Inflammatory processes have adverse effects on vision by affecting photoreceptor-bearing cells that do not regenerate. This study aimed at characterizing inflammatory CD4+ and CD8+ T cell subsets in the peripheral blood of active and inactive BSRCs. Furthermore, we correlated phenotypical and functional immunological analyses with clinical data. We observed a slight increase of terminally differentiated effector memory CD8+ T cells expressing CD45RA (TEMRA) in blood of inactive, compared to active BSRCs. Moreover, we identified a trend for a decreased population of TH2 cells and increased TH1 frequencies in active BSRCs, a typical sign of ongoing autoimmune processes. Functional assays demonstrated severe and overall impairment of effector function of both, CD4+ and CD8+ inflammatory T cells, which might reflect T cell exhaustion. Although the eye is the main site of inflammation in BSRC, we observed altered T cell subset compositions in the peripheral blood, dependent on the disease status. Our results indicate that T cells may play a major role in BSRC pathology, although our cohort size is too limited for definitve conclusions. Future studies with larger BSRCs have to be performed.

scholarly journals Quantitative assessment of the pool size and subset distribution of cytolytic T lymphocytes within human resting or alloactivated peripheral blood T cell populations.

1983 ◽  
Vol 158 (2) ◽  
pp. 571-585 ◽  
Author(s):  
A Moretta ◽  
G Pantaleo ◽  
L Moretta ◽  
M C Mingari ◽  
J C Cerottini
Keyword(s):  
Monoclonal Antibody ◽  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Peripheral Blood ◽  
Great Majority ◽  
T Cell Subsets ◽  
Cytolytic T Lymphocytes ◽  
Subset Distribution

In order to directly assess the distribution of cytolytic T lymphocytes (CTL) and their precursors (CTL-P) in the two major subsets of human T cells, we have used limiting dilution microculture systems to determine their frequencies. The two subsets were defined according to their reactivity (or lack thereof) with B9.4 monoclonal antibody (the specificity of which is similar, if not identical, to that of Leu 2b monoclonal antibody). Both B9+ and B9- cells obtained by sorting peripheral blood resting T cells using the fluorescence-activated cell sorter (FACS) were assayed for total CTL-P frequencies in a microculture system that allows clonal growth of every T cell. As assessed by a lectin-dependent assay, approximately 30% of peripheral blood T cells were CTP-P. In the B9+ subset (which represents 20-30% of all T cells), the CTL-P frequency was close to 100%, whereas the B9- subset had a 25-fold lower CTL-P frequency. It is thus evident that 90% and 10% of the total CTL-P in peripheral blood are confined to the B9+ or B9- T cell subsets, respectively. Analysis of the subset distribution of CTL-P directed against a given set of alloantigens confirmed these findings. CTL-P frequencies were also determined in B9+ and B9- subsets derived from T cells that had been activated in allogenic mixed leucocyte cultures (MLC). Approximately 10% of MLC T cells were CTL-P. This frequency was increased 3.5-fold in the B9+ subset, whereas the B9- subset contained only a small, although detectable number of CTL-P. Moreover, the great majority of the (operationally defined) CTL-P in MLC T cell population were found to be directed against the stimulating alloantigens, thus indicating a dramatic increase in specific CTL-P frequencies following in vitro stimulation in bulk cultures.

scholarly journals The Transcriptional Differences of Avian CD4+CD8+ Double-Positive T Cells and CD8+ T Cells From Peripheral Blood of ALV-J Infected Chickens Revealed by Smart-Seq2

2021 ◽  
Vol 11 ◽  
Author(s):  
Manman Dai ◽  
Li Zhao ◽  
Ziwei Li ◽  
Xiaobo Li ◽  
Bowen You ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Signaling Pathway ◽  
Cell Population ◽  
Peripheral Blood ◽  
T Cell Response ◽  
T Cell Subsets ◽  
High Expression ◽  
Receptor Interaction ◽  
Double Positive

It is well known that chicken CD8+ T cell response is vital to clearing viral infections. However, the differences between T cell subsets expressing CD8 receptors in chicken peripheral blood mononuclear cells (PBMCs) have not been compared. Herein, we used Smart-Seq2 scRNA-seq technology to characterize the difference of chicken CD8high+, CD8high αα+, CD8high αβ+, CD8medium+, and CD4+CD8low+ T cell subsets from PBMCs of avian leukosis virus subgroup J (ALV-J)-infected chickens. Weighted gene co-expression network analysis (WGCNA) and Trend analysis revealed that genes enriched in the “Cytokine–cytokine receptor interaction” pathway were most highly expressed in the CD8high αα+ T cell population, especially T cell activation or response-related genes including CD40LG, IL2RA, IL2RB, IL17A, IL1R1, TNFRSF25, and TNFRSF11, suggesting that CD8high αα+ T cells rather than other CD8 subpopulations were more responsive to ALV-J infections. On the other hand, genes involved in the “FoxO signaling pathway” and “TGF-beta signaling pathway” were most highly expressed in the CD4+CD8low+ (CD8low+) T cell population and the function of CD4+CD8low+ T cells may play roles in negatively regulating the functions of T cells based on the high expression of CCND1, ROCK1, FOXO1, FOXO3, TNFRSF18, and TNFRSF21. The selected gene expressions in CD8+ T cells and CD4+CD8low+ double-positive T cells confirmed by qRT-PCR matched the Smart-Seq2 data, indicating the reliability of the smart-seq results. The high expressions of Granzyme K, Granzyme A, and CCL5 indicated the positive response of CD8+ T cells. Conversely, CD4+CD8+ T cells may have the suppressor activity based on the low expression of activation molecules but high expression of T cell activity suppressor genes. These findings verified the heterogeneity and transcriptional differences of T cells expressing CD8 receptors in chicken PBMCs.

scholarly journals T-cell-subset characterization of human T-CLL

Blood ◽  
1979 ◽  
Vol 53 (6) ◽  
pp. 1066-1075 ◽  
Author(s):  
EL Reinherz ◽  
LM Nadler ◽  
DS Rosenthal ◽  
WC Moloney ◽  
SF Schlossman
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Cells ◽  
Peripheral Blood ◽  
Lymphoblastic Leukemia ◽  
Cell Subset ◽  
T Cell Subsets ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Human T Cell ◽  
Malignant T Cells

Abstract Circulating peripheral blood tumor cells in four cases of chronic lymphoproliferative disease were immunologically characterized. By the use of T-cell-specific heteroantisera and indirect immunofluorescence, all were shown to involve proliferation of malignant T cells. Three cases demonstrated morphologic and clinical features consistent with chronic lymphocytic leukemia (CLL), and one case presented as a lymphosarcoma cell leukemia. Antisera specific for normal human T-cell subsets defined the malignant T cells in each case as arising from the TH2--subset. This subset normally constitutes approximately 80% of human peripheral blood T cells. Terminal deoxynucleotidyl transferase (TdT) was not detected in any of the T-cell CLL cases, thus supporting the notion that T-cell CLL represents a malignancy of a mature phenotype. The one patient with lymphosarcoma whose tumor cells were TdT-positive subsequently developed T-cell acute lymphoblastic leukemia (ALL). Moreover, la-like antigen (p23,30) was detected on two of these tumor cell populations. In addition, it was shown that not all tumor cells were E-rosette-positive, since only cells from 3 of 4 patients were capable of forming spontaneous rosettes. These findings demonstrate that heteroantisera can provide an additional important tool for dissecting the heterogeneity of T-cell leukemias and for relating them to more differentiated normal T cells.

scholarly journals Characterization of Avian γδ T-Cell Subsets afterSalmonella entericaSerovar Typhimurium Infection of Chicks

2010 ◽  
Vol 79 (2) ◽  
pp. 822-829 ◽  
Author(s):  
Jana Pieper ◽  
Ulrich Methner ◽  
Angela Berndt
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
Fas Ligand ◽  
Interleukin 2 ◽  
Cell Subset ◽  
Immune Defense ◽  
T Cell Subsets ◽  
Mrna Levels ◽  
Γδ T Cell ◽  
Ifn Γ

ABSTRACTAvian γδ T lymphocytes are frequently found in blood and organs and are assumed to be crucial to the immune defense againstSalmonellainfections of chicks. To elucidate the so-far-unknown immunological features of subpopulations of avian γδ T cells in the course of infection, day-old chicks were infected orally withSalmonella entericaserovar Typhimurium. Until 11 days after infection, the occurrence as well as transcription of the CD8 antigen and immunologically relevant protein genes of CD8α−and CD8α+high(CD8αα+CD8αβ+) γδ cells were analyzed using flow cytometry and quantitative real-time reverse transcription-PCR (RT-PCR) with blood, spleen, thymus, and cecum samples. After infection, an increased percentage of CD8α+highγδ T lymphocytes was found in blood, in spleen, and, with the highest values and most rapidly, in cecum. Within the CD8α+highsubset, a significant rise in the number of CD8αα+cells was accompanied by enhanced CD8α antigen expression and reduced gene transcription of the CD8β chain. CD8αα+and CD8αβ+cells showed elevated transcription for Fas, Fas ligand (FasL), interleukin-2 receptor α (IL-2Rα), and gamma interferon (IFN-γ). While the highest fold changes in mRNA levels were observed in CD8αβ+cells, the mRNA expression rates of CD8αβ+cells never significantly exceeded those of the CD8αα+cells. In conclusion, both CD8α+highγδ T-cell subpopulations (CD8αα+and CD8αβ+) might be a potential source of IFN-γ inSalmonella-infected chicks. However, due to their prominent frequency in blood and organs after infection, the avian CD8αα+γδ T-cell subset seems to be unique and of importance in the course ofSalmonellaTyphimurium infection of very young chicks.

Phenotypic and Functional Analysis of T-Cells Mobilized in HLA-Matched Sibling Donors Following Treatment with the Chemokine Antagonist AMD3100.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3001-3001 ◽  
Author(s):  
Michael Rettig ◽  
Steven M. Devine ◽  
Julie Ritchey ◽  
John F. DiPersio
Keyword(s):  
T Cells ◽  
T Cell ◽  
Peripheral Blood ◽  
Acute Gvhd ◽  
T Cell Subsets ◽  
Effector Memory ◽  
Phenotypic Properties ◽  
Functional Changes ◽  
Cd8 Cells ◽  
Matched Sibling

Abstract We are currently evaluating a novel method for the procurement of peripheral blood stem cells from HLA matched sibling donors using a direct antagonist of the CXCR4/SDF-1 interaction called AMD3100 (A). Donors receive a single subcutaneous injection of A and then undergo a 20 liter leukapheresis (LP) four hours later. The LP product is then cryopreserved and subsequently transplanted following ablative conditioning. To date, we have performed 15 transplants with allografts collected following A alone. In comparison to allografts collected following five days of G-CSF, A mobilized allografts contain approximately 50% less CD34+ cells but 2–3 times more CD3+ cells. Nevertheless, the kinetics of neutrophil and platelet engraftment have been virtually identical to that observed following G-mobilized allografts and grades 2–4 acute GVHD has been observed in only 20% of recipients. We sought to analyze the functional and phenotypic properties of T cells collected following A alone to understand the relatively low rates of acute GVHD despite the transplantation of higher T-cell doses. In 3 donors, extensive T cell phenotyping was performed on donor peripheral blood prior to A, 6 hours following A, and also on the LP product collected after A. Specifically, we were seeking to determine whether any alteration in CD4+ or CD8+ subsets had occurred. We analyzed T-cell subsets using well described markers for central memory, effector memory, naïve, and effector memory RA phenotypes. We also assessed expression of CD62L, CD127, CCR7, and SLAM family members (CD48, CD150, and CD244) on both CD4+ and CD8+ cells. The activation status on CD4 and CD8 cells was assessed using markers for CD25, CD30, and CD69. Finally we assessed for quantitative changes in the mobilization of regulatory T cells by assaying the proportion of CD4+CD25+FoxP3+ cells mobilized following A. In none of these analyses could we detect any significant alteration in the relative ratios of CD4 or CD8 subsets mobilized by A. Finally, the functional capacity of purified CD3+ cells collected following A was assessed using a NOD/SCID xenogeneic GVHD model we have recently developed. In that model, survival of mice transplanted with A mobilized T-cells was similar to that observed with untreated T cells, suggesting that A mobilized T cells retain their GVHD-inducing capacity. In summary, these preliminary data suggest that AMD3100 induces a “pan-mobilization” of T cell subsets without any apparent skewing toward a particular subset. These studies are in contrast to others suggesting subtle phenotypic and functional changes in donor T cells after mobilization with G-CSF. Further studies evaluating A mobilized allografts are ongoing.

scholarly journals Interplay between IL-10, IFN-γ, IL-17A and PD-1 Expressing EBNA1-Specific CD4+ and CD8+ T Cell Responses in the Etiologic Pathway to Endemic Burkitt Lymphoma

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5375
Author(s):  
Catherine S. Forconi ◽  
David H. Mulama ◽  
Priya Saikumar Lakshmi ◽  
Joslyn Foley ◽  
Juliana A. Otieno ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Burkitt Lymphoma ◽  
Cd4 T Cells ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
T Cell Subsets ◽  
Effector Memory ◽  
Healthy Children ◽  
Ifn Γ

Children diagnosed with endemic Burkitt lymphoma (eBL) are deficient in interferon-γ (IFN-γ) responses to Epstein–Barr Nuclear Antigen1 (EBNA1), the viral protein that defines the latency I pattern in this B cell tumor. However, the contributions of immune-regulatory cytokines and phenotypes of the EBNA1-specific T cells have not been characterized for eBL. Using a bespoke flow cytometry assay we measured intracellular IFN-γ, IL-10, IL-17A expression and phenotyped CD4+ and CD8+ T cell effector memory subsets specific to EBNA1 for eBL patients compared to two groups of healthy children with divergent malaria exposures. In response to EBNA1 and a malaria antigen (PfSEA-1A), the three study groups exhibited strikingly different cytokine expression and T cell memory profiles. EBNA1-specific IFN-γ-producing CD4+ T cell response rates were lowest in eBL (40%) compared to children with high malaria (84%) and low malaria (66%) exposures (p < 0.0001 and p = 0.0004, respectively). However, eBL patients did not differ in CD8+ T cell response rates or the magnitude of IFN-γ expression. In contrast, eBL children were more likely to have EBNA1-specific CD4+ T cells expressing IL-10, and less likely to have polyfunctional IFN-γ+IL-10+ CD4+ T cells (p = 0.02). They were also more likely to have IFN-γ+IL-17A+, IFN-γ+ and IL-17A+ CD8+ T cell subsets compared to healthy children. Cytokine-producing T cell subsets were predominantly CD45RA+CCR7+ TNAIVE-LIKE cells, yet PD-1, a marker of persistent activation/exhaustion, was more highly expressed by the central memory (TCM) and effector memory (TEM) T cell subsets. In summary, our study suggests that IL-10 mediated immune regulation and depletion of IFN-γ+ EBNA1-specific CD4+ T cells are complementary mechanisms that contribute to impaired T cell cytotoxicity in eBL pathogenesis.

scholarly journals T-cell-subset characterization of human T-CLL

Blood ◽  
1979 ◽  
Vol 53 (6) ◽  
pp. 1066-1075
Author(s):  
EL Reinherz ◽  
LM Nadler ◽  
DS Rosenthal ◽  
WC Moloney ◽  
SF Schlossman
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Cells ◽  
Peripheral Blood ◽  
Lymphoblastic Leukemia ◽  
Cell Subset ◽  
T Cell Subsets ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Human T Cell ◽  
Malignant T Cells

Circulating peripheral blood tumor cells in four cases of chronic lymphoproliferative disease were immunologically characterized. By the use of T-cell-specific heteroantisera and indirect immunofluorescence, all were shown to involve proliferation of malignant T cells. Three cases demonstrated morphologic and clinical features consistent with chronic lymphocytic leukemia (CLL), and one case presented as a lymphosarcoma cell leukemia. Antisera specific for normal human T-cell subsets defined the malignant T cells in each case as arising from the TH2--subset. This subset normally constitutes approximately 80% of human peripheral blood T cells. Terminal deoxynucleotidyl transferase (TdT) was not detected in any of the T-cell CLL cases, thus supporting the notion that T-cell CLL represents a malignancy of a mature phenotype. The one patient with lymphosarcoma whose tumor cells were TdT-positive subsequently developed T-cell acute lymphoblastic leukemia (ALL). Moreover, la-like antigen (p23,30) was detected on two of these tumor cell populations. In addition, it was shown that not all tumor cells were E-rosette-positive, since only cells from 3 of 4 patients were capable of forming spontaneous rosettes. These findings demonstrate that heteroantisera can provide an additional important tool for dissecting the heterogeneity of T-cell leukemias and for relating them to more differentiated normal T cells.

scholarly journals A possible role of immunopathogenesis in COVID-19 progression

2020 ◽  
Author(s):  
Moritz Anft ◽  
Krystallenia Paniskaki ◽  
Arturo Blazquez-Navarro ◽  
Adrian Doevelaar ◽  
Felix S. Seibert ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Humoral Immunity ◽  
Viral Infections ◽  
Cell Subset ◽  
T Cell Response ◽  
T Cell Subsets ◽  
Clear Correlation

AbstractBackgroundThe efficacy of the humoral and cellular immunity determines the outcome of viral infections. An appropriate immune response mediates protection, whereas an overwhelming immune response has been associated with immune-mediated pathogenesis in viral infections. The current study explored the general and SARS-CoV-2 specific cellular and humoral immune status in patients with different COVID-19 severities.MethodsIn this prospective study, we included 53 patients with moderate, severe, and critical COVID-19 manifestations comparing their quantitative, phenotypic, and functional characteristics of circulating immune cells, SARS-CoV-2 antigen specific T-cells, and humoral immunity.ResultsSignificantly diminished frequencies of CD8+T-cells, CD4+ and CD8+T-cell subsets with activated differentiated memory/effector phenotype and migratory capacity were found in circulation in patients with severe and/or critical COVID-19 as compared to patients with moderate disease. Importantly, the improvement of the clinical courses from severe to moderate was accompanied by an improvement in the T-cell subset alterations. Furthermore, we surprisingly observed a detectable SARS-CoV-2-reactive T-cell response in all three groups after stimulation with SARS-CoV-2 S-protein overlapping peptide pool already at the first visit. Of note, patients with a critical COVID-19 demonstrated a stronger response of SARS-CoV-2-reactive T-cells producing Th1 associated inflammatory cytokines. Furthermore, clear correlation between antibody titers and SARS-CoV-2-reactive CD4+ frequencies underscore the role of specific immunity in disease progression.ConclusionOur data demonstrate that depletion of activated memory phenotype circulating T-cells and a strong SARS-CoV-2-specific cellular and humoral immunity are associated with COVID-19 disease severity. This counter-intuitive finding may have important implications for diagnostic, therapeutic and prophylactic COVID-19 management.

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