scholarly journals Prolonged enhancement of cytotoxic T lymphocytes in the post-recovery state of severe COVID-19

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Yumi Mitsuyama ◽  
Kazuma Yamakawa ◽  
Katsuhide Kayano ◽  
Miho Maruyama ◽  
Takeshi Wada ◽  
...  

AbstractWe evaluated the peripheral blood immune responses of lymphocytes in severe Coronavirus disease 2019 (COVID-19) patients in different stages of recovery using single-cell mass cytometry. The patients with prolonged hospitalization did not show recovery of B lymphocyte counts and CD4-positive T lymphocyte counts but did show abundant CD8-positive T lymphocytes. CD4 and CD8 T cells expressing high levels of T-bet and Granzyme B were more abundant in post-recovery patients. This study showed that cytotoxic Th1 and CD8 T cells are recruited to the peripheral blood long after recovery from COVID-19.

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi103-vi104
Author(s):  
Hairong Wang ◽  
Cheng-Cheng Guo ◽  
Hongyu Chen ◽  
Yang Qun-ying ◽  
Zhong-ping Chen

Abstract OBJECTIVE This study was designed to retrospectively analyze the dynamic changes of peripheral blood lymphocyte subsets and prognosis among patients with intracranial germ cell tumors. METHODS A total of 150 intracranial germ cell tumors patients diagnosed between June 2011 till November 2019 were retrospectively investigated. Peripheral blood total T lymphocytes (CD3+) percentage, T helper/inducible lymphocytes(CD3+CD4+)percentage, T inhibitory/toxic lymphocytes (CD3+CD8+) percentage, B lymphocyte (CD19+) percentage, NK lymphocyte (CD3/CD16+CD56+) percentage, regulatory T cells (CD4+CD25+,CD8+CD25+), and T helper/toxic lymphocyte ratio (CD4+/CD8+ ratio) were quantified by flow cytometry analysis. Clinical information was extracted from the database in Sun Yat-sen University Cancer Center and survival data was confirmed through outpatient visits and telephone follow-up. RESULTS T lymphocytes population was increased after anti-tumor treatment, with significant difference of total T lymphocytes (CD3+), inhibitory/toxic T cells (CD3+CD8+) and regulatory T cells (CD4+CD25+ and CD8+CD25+), (p=0.008, p=0.000, p=0.008 and p=0.001 respectively), while B lymphocytes(CD19+) decreased after chemotherapy(p=0.003). The dynamic levels of T lymphocyte and B lymphocyte subpopulation after chemotherapy did not present significant differences between gender, age, and locations of tumors (p >0.05), except CD4+CD25+ T cells in younger children (age< 16 years older) increased significantly than the elder (age >16), p=0.04. Patients with increased CD19+ B cells presented significant suboptimal outcomes compared with the no increased (p=0.024). Similarly, increased CD3+ T cells, CD3+CD8+ T cells, CD4+CD25+ T cells reduced the risk of death (p=0.006, p=0.019, p=0.042 respectively). Multivariate Cox Regression analysis showed: increased CD19+ B cells, p=0.04, HR=1.688, 95%CI=1.025-2.779. CONCLUSION After anti-tumor treatment, cell-mediated immunity activated, enhanced, and dominated in anti-tumor response. An increased level of CD19+ subsets was an independent predictor for inferior overall survival. Systemic circulating T cells immunity played an important role and mediating antitumor responses may pave the road for new immunity strategies.


2019 ◽  
Vol 200 ◽  
pp. 24-30 ◽  
Author(s):  
Min Sun Shin ◽  
Kristina Yim ◽  
Kevin Moon ◽  
Hong-Jai Park ◽  
Subhasis Mohanty ◽  
...  

2007 ◽  
Vol 103 (1) ◽  
pp. 396-401 ◽  
Author(s):  
Richard J. Simpson ◽  
Geraint D. Florida-James ◽  
Cormac Cosgrove ◽  
Greg P. Whyte ◽  
Scott Macrae ◽  
...  

Clonal expansion of T lymphocytes in response to antigenic stimulation is a fundamental process of adaptive immunity. As a consequence of clonal expansion, some T lymphocytes acquire a senescent phenotype, fail to replicate in response to further antigenic stimulation, and express the killer cell lectin-like receptor G1 (KLRG1) and/or CD57. Physical exercise elicits a mobilization of large numbers of T lymphocytes into the bloodstream from peripheral lymphoid compartments, but the frequency of senescent cells in the mobilized population is not known. Eight male runners (age: 29 ± 9 yr; maximal O2 uptake 62 ± 6 ml·kg−1·min−1) performed an intensive treadmill-running protocol at 80% maximal O2 uptake to volitional exhaustion. Blood lymphocytes isolated before, immediately after, and 1 h after exercise were assessed for cell surface expression of KLRG1, CD57, CD28, CD45RA, CD45RO, CD62L, and lymphocyte subset markers (CD3, CD4, CD8, CD56) by flow cytometry. The percentage of all CD3+ T lymphocytes expressing KLRG1 and CD57 increased with exercise ( P < 0.01). The change in T-lymphocyte KLRG1 expression was attributed to both CD4+ and CD8 bright T cells, with the relative change being greater for the CD8 bright population ( P < 0.01). Mobilized T-lymphocyte populations expressing KLRG1 and CD57 appeared to extravasate the peripheral blood compartment after 1 h of recovery. In conclusion, T lymphocytes with a senescent phenotype are mobilized and subsequently removed from the bloodstream in response to acute high-intensity exercise. This suggests that T lymphocytes contained within the peripheral lymphoid compartments that are mobilized by exercise are likely to be at a more advanced stage of biological aging and have a reduced capacity for clonal expansion than blood-resident T cells.


Blood ◽  
1992 ◽  
Vol 80 (12) ◽  
pp. 3157-3163
Author(s):  
I Bank ◽  
M Book ◽  
L Cohen ◽  
A Kneller ◽  
E Rosental ◽  
...  

CD8+ T-lymphocyte populations may be expanded in the peripheral blood of patients with chronic idiopathic neutropenia and may be involved in suppression of granulopoiesis. In this report, we have analyzed the T-cell receptor (TCR) used by the T lymphocytes of a patient with chronic severe neutropenia. Using specific oligonucleotides in the polymerase chain reaction (PCR) to amplify cDNA specific for the different families of the V alpha, V beta, and V delta TCR genes, and monoclonal antibodies (MoAbs) to examine T-lymphocyte subsets and their TCR, a persistent expansion of CD3+CD8+ T lymphocytes and a reduced repertoire of TCR V alpha and V beta genes were found in the patient's peripheral blood mononuclear cell (PBMC) preparations. A predominant portion of the T lymphocytes expressed a unique TCR structure. Thus, we found that, despite the fact that 98% of the T cells expressed alpha beta TCR on the surface membrane and less than 2% expressed tau delta TCR, nonetheless, 40% to 60% of the T cells stained positively with anti V delta 1 MoAb. Using the PCR analysis, the V delta 1 gene segment was found to be rearranged to C alpha, rather than to C delta genes. The expanded C alpha V delta 1+ cells, which are found only rarely in normal PB, expressed CD8 and were cytotoxic, and the C alpha V delta 1 receptor was functional in cytotoxicity. This constitutes the first description of an expansion of cytotoxic CD8+ lymphocytes expressing a functional “hybrid” C alpha V delta 1 gene in vivo, and suggests a pathogenic role for CD8+ C alpha V delta 1+ cells in some patients with idiopathic neutropenia.


2019 ◽  
Vol 69 (10) ◽  
pp. 1752-1756 ◽  
Author(s):  
Govindakarnavar Arunkumar ◽  
Santhosha Devadiga ◽  
Anita K McElroy ◽  
Suresh Prabhu ◽  
Shahin Sheik ◽  
...  

Abstract Background Nipah virus (NiV) is 1 of 10 potential causes of imminent public health emergencies of international concern. We investigated the NiV outbreak that occurred in May 2018 in Kerala, India. Here we describe the longitudinal characteristics of cell-mediated and humoral immune responses to NiV infection during the acute and convalescent phases in 2 human survivors. Methods Serial blood samples were obtained from the only 2 survivors of the NiV outbreak in Kerala. We used flow cytometry to determine the absolute T-lymphocyte and B-lymphocyte counts and the phenotypes of both T and B cells. We also detected and quantitated the humoral immune response to NiV by virus-specific immunoglobulin M (IgM) and immunoglobulin G (IgG) enzyme-linked immunosorbent assay. Results Absolute numbers of T lymphocytes remained within normal limits throughout the period of illness studied in both survivors. However, a marked elevation of activated CD8 T cells was observed in both cases. More than 30% of total CD8 T cells expressed Ki67, indicating active proliferation. Proliferating (Ki-67+) CD8 T cells expressed high levels of granzyme B and PD-1, consistent with the profile of acute effector cells. Total B-lymphocyte, activated B-cell, and plasmablast counts were also elevated in NiV survivors. These individuals developed detectable NiV-specific IgM and IgG antibodies within a week of disease onset. Clearance of NiV RNA from blood preceded the appearance of virus-specific IgG and coincided with the peak of activated CD8 T cells. Conclusions We describe for the first time longitudinal kinetic data on the activation status of human B- and T-cell populations during acute NiV infection. While marked CD8 T-cell activation was observed with effector characteristics, activated CD4 T cells were less prominent.


Blood ◽  
1993 ◽  
Vol 81 (8) ◽  
pp. 2085-2092 ◽  
Author(s):  
TL Whiteside ◽  
EM Elder ◽  
D Moody ◽  
J Armstrong ◽  
M Ho ◽  
...  

Abstract Cytolytic T lymphocytes play an important role in host defense against viral infections, including human immunodeficiency virus (HIV). In a phase I clinical trial (protocol 080 of the AIDS Clinical Trials Group), generation of CD8+ effector cells from peripheral blood of patients with acquired immunodeficiency syndrome (AIDS)-related complex (ARC) or AIDS and safety of autologous adoptive transfer of these cells were evaluated. For therapeutic infusions, CD8+ T cells were purified by positive selection on anti-CD8 monoclonal antibody-coated flasks from leukapheresed peripheral blood of seven patients. These CD8+ T cells were cultured in the presence of interleukin-2 and phytohemagglutinin for up to 3 weeks to obtain cells sufficient for therapeutic infusions (10(8) to 10(10)). All 31 cell cultures established from the seven patients and used for therapy were highly enriched in CD8+ (mean, 97%), CD8+HLA-DR+ (50%), cytotoxic CD8+CD11b- (82%), and memory CD29+ (78%) T lymphocytes. In vitro expanded CD8+ cells had excellent cytotoxic function at the time they were used for therapy, including HIV-specific activity against autologous targets infected with vaccinia vectors expressing HIV-IIIb antigens, gag, pol, and env. Anti-HIV activity of cultured CD8+ cells was significantly higher than that of autologous fresh peripheral blood lymphocytes. Our results show that CD8+ T lymphocytes obtained from peripheral blood of symptomatic HIV-infected patients can be purified, cultured to obtain large numbers of cells with enhanced anti-HIV activity, and safely infused into patients with AIDS as a form of immunotherapy.


2015 ◽  
Vol 68 (10) ◽  
pp. 812-818 ◽  
Author(s):  
Elysia M S Tan ◽  
Tinte Itinteang ◽  
Daria A Chudakova ◽  
Jonathan C Dunne ◽  
Reginald Marsh ◽  
...  

AimsInterstitial CD45+ cells and T lymphocytes have previously been demonstrated within infantile haemangioma (IH). This study investigated the expression of B and T lymphocyte markers by the CD45+ population, and the expression of Thy-1, a marker of thymocyte progenitors, which have the ability to give rise to both B and T cells.MethodsImmunohistochemical (IHC) staining was performed on proliferating and involuted IHs for the expression of CD45, CD3, CD20, CD79a, Thy-1 and CD34. The presence of mRNA corresponding to CD45, CD3G, CD20 and Thy-1 was confirmed by reverse transcriptase-polymerase chain reaction in snap-frozen IH tissues. Cell counting of 3,3-diaminobenzidine IHC-stained slides was performed on CD45+ only cells and dually stained CD45+/CD3+ cells or CD45+/CD20+ cells and analysed statistically. In situ hybridisation and mass spectrometry were also performed to confirm the presence and abundance of Thy-1, respectively.ResultsIHC staining showed a subpopulation of CD45+ interstitial cells that expressed the T lymphocyte marker, CD3, and another subpopulation that expressed the B lymphocyte marker, CD20, in proliferating and diminished in involuted IHs. The abundant expression of Thy-1 on the endothelium of proliferating, but not involuted IH, was demonstrated by IHC staining and confirmed by in situ hybridisation and mass spectrometry.ConclusionsBoth B and T lymphocytes are present within the interstitium of proliferating and involuted IH. The expression of Thy-1 by the endothelium suggests that B and T cells in IH may have originated from within the lesion, rather than migrating from the peripheral circulation.


Blood ◽  
1992 ◽  
Vol 80 (12) ◽  
pp. 3157-3163 ◽  
Author(s):  
I Bank ◽  
M Book ◽  
L Cohen ◽  
A Kneller ◽  
E Rosental ◽  
...  

Abstract CD8+ T-lymphocyte populations may be expanded in the peripheral blood of patients with chronic idiopathic neutropenia and may be involved in suppression of granulopoiesis. In this report, we have analyzed the T-cell receptor (TCR) used by the T lymphocytes of a patient with chronic severe neutropenia. Using specific oligonucleotides in the polymerase chain reaction (PCR) to amplify cDNA specific for the different families of the V alpha, V beta, and V delta TCR genes, and monoclonal antibodies (MoAbs) to examine T-lymphocyte subsets and their TCR, a persistent expansion of CD3+CD8+ T lymphocytes and a reduced repertoire of TCR V alpha and V beta genes were found in the patient's peripheral blood mononuclear cell (PBMC) preparations. A predominant portion of the T lymphocytes expressed a unique TCR structure. Thus, we found that, despite the fact that 98% of the T cells expressed alpha beta TCR on the surface membrane and less than 2% expressed tau delta TCR, nonetheless, 40% to 60% of the T cells stained positively with anti V delta 1 MoAb. Using the PCR analysis, the V delta 1 gene segment was found to be rearranged to C alpha, rather than to C delta genes. The expanded C alpha V delta 1+ cells, which are found only rarely in normal PB, expressed CD8 and were cytotoxic, and the C alpha V delta 1 receptor was functional in cytotoxicity. This constitutes the first description of an expansion of cytotoxic CD8+ lymphocytes expressing a functional “hybrid” C alpha V delta 1 gene in vivo, and suggests a pathogenic role for CD8+ C alpha V delta 1+ cells in some patients with idiopathic neutropenia.


Blood ◽  
1993 ◽  
Vol 81 (8) ◽  
pp. 2085-2092
Author(s):  
TL Whiteside ◽  
EM Elder ◽  
D Moody ◽  
J Armstrong ◽  
M Ho ◽  
...  

Cytolytic T lymphocytes play an important role in host defense against viral infections, including human immunodeficiency virus (HIV). In a phase I clinical trial (protocol 080 of the AIDS Clinical Trials Group), generation of CD8+ effector cells from peripheral blood of patients with acquired immunodeficiency syndrome (AIDS)-related complex (ARC) or AIDS and safety of autologous adoptive transfer of these cells were evaluated. For therapeutic infusions, CD8+ T cells were purified by positive selection on anti-CD8 monoclonal antibody-coated flasks from leukapheresed peripheral blood of seven patients. These CD8+ T cells were cultured in the presence of interleukin-2 and phytohemagglutinin for up to 3 weeks to obtain cells sufficient for therapeutic infusions (10(8) to 10(10)). All 31 cell cultures established from the seven patients and used for therapy were highly enriched in CD8+ (mean, 97%), CD8+HLA-DR+ (50%), cytotoxic CD8+CD11b- (82%), and memory CD29+ (78%) T lymphocytes. In vitro expanded CD8+ cells had excellent cytotoxic function at the time they were used for therapy, including HIV-specific activity against autologous targets infected with vaccinia vectors expressing HIV-IIIb antigens, gag, pol, and env. Anti-HIV activity of cultured CD8+ cells was significantly higher than that of autologous fresh peripheral blood lymphocytes. Our results show that CD8+ T lymphocytes obtained from peripheral blood of symptomatic HIV-infected patients can be purified, cultured to obtain large numbers of cells with enhanced anti-HIV activity, and safely infused into patients with AIDS as a form of immunotherapy.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1264-1264
Author(s):  
Tomohiro Kozako ◽  
Masaki Akimoto ◽  
Izumi Masamoto ◽  
Makoto Yoshimitsu ◽  
Kakushi Matsushita ◽  
...  

Abstract Human T-cell lymphotropic virus type 1 (HTLV-1)-specific CTL are thought to be immune effectors that reduce the risk of adult T-cell leukemia (ATL). However, in vivo conditions of anti-HTLV-1 CTL before and after ATL development have yet to be determined. To characterize anti-HTLV-1 CTL in asymptomatic HTLV-1 carriers (AC) and ATL patients, we analyzed the frequency and diversity of HTLV-1-specific CD8+ T cells in PBMC of 35 AC and 32 ATL patients using 16 distinct epitopes of HTLV-1 Tax or Env/HLA tetramers along with intracellular cytolytic effector molecules (IFN-γ , perforin, and granzyme B). Overall frequency of subjects possessing Tax-specific CD8+ T cells was significantly lower in ATL than AC (53% vs. 90%, p &lt; 0.001) whereas the difference in Env-specific CD8+ T cells was not statistically significant. AC possessed Tax11-19/HLA-A*0201-specific tetramer+ cells by 90% and Tax301-309/HLA-A*2402-specific tetramer+ cells by 92%. Some AC recognized more than one epitope. In contrast, ATL recognized only Tax 11-19 with HLA-A*0201 and Tax301-309 with HLA-A*2402 at frequencies of 30% and 55%. There were also significant differences in percentage of cells binding Tax11-19/HLA-A*0201, Tax301-309/HLA-A*2402, and CMV/HLA tetramers between AC and ATL. Anti-HTLV-1 Tax CD8+ T cells in AC and ATL produced IFN-γ in response to Tax. Contrarily, perforin and granzyme B expression in anti-HTLV-1 CD8+ T cells of ATL was significant lower than that of AC, but no differences in anti-CMV CD8+ T cells. In addition, expression of perforin and granzyme B in HTLV-1 Tax tetramer+/CD8+ T lymphocytes were diminished in comparison to those in CMV tetramer+/CD8+ T lymphocytes in both AC and ATL. Frequency of Tax-specific CD8+ T cells in AC were related with proviral load in HLA-A*0201. These results suggest that our HTLV-1/HLA tetramer assay enabled analysis of anti-HTLV-1 CD8+ T cells in PBMC of AC and ATL patients and demonstrated deletion of anti-Tax CD8+ T cells in ATL patients. Intracellular cytokine expression in anti-HTLV-1 CD8+ T cells had significant difference between AC and ATL, but not in anti-CMV CD8+ T cells. The reduced frequency, diversity, and function of anti-HTLV-1 Tax CD8+ T cell clones may be related to the development of ATL. This HLA tetramer assay can be used for monitoring the in vivo status of CTL and it may be possible to identify the high risk group in AC of developing to ATL. Summary of HTLV-1-specific tetramer and HTLV-1 proviral load in AC and ATL patients AC ATL †The number of subject positive for tetramers; the percentage of HTLV-1/HLA tetramer+/CD8+ T cells in the CD8+/CD45+ T lymphocytes &gt; 0.1% are counted as subject positives for tetramer. ††The HTLV-1 proviral load is the ± S.E., copies/1000 PBMC. *p &lt; 0.001; **p &lt; 0.05, Significant differences between AC and ATL. Subjects positive for Tax tetramer† 28 (n = 31) 15 (n = 28) * Subjects positive for Env tetramer† 4 (n = 31) 0 (n = 28) Tax11-19 tetramer+ CD8+ T cells† 9 (n = 10) 3 (n = 10) ** Tax301-309 tetramer+ CD8+ T cells† 22 (n = 24) 12 (n = 22) * HTLV-1 proviral load†† 65.4 ± 7.4 (n = 35) 1095.4 ± 194.1 (n = 29) *


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