Effects of Adoptive Immunotherapy with Autologous CD8+ T Lymphocytes on Immunologic Parameters: Lymphocyte Subsets and Cytotoxic Activity

1993 ◽  
Vol 68 (3) ◽  
pp. 263-272 ◽  
Author(s):  
David Torpey ◽  
Xiao-Li Huang ◽  
John Armstrong ◽  
Monto Ho ◽  
Theresa Whiteside ◽  
...  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hao Kang ◽  
Yunbo Wei ◽  
Ming Liu ◽  
Di Yu ◽  
Yong Tao

Abstract Background The purpose of this study is to investigate the aqueous humor (AH) T lymphocyte subsets and cytokines of acute retinal necrosis (ARN) to elucidate the immunologic inflammatory features of this disorder. Methods Three patients with ARN infected with varicella zoster virus (VZV) who underwent multiple intravitreal injections of ganciclovir were enrolled in this study. The control group consisted of four non-infectious patients with acute anterior uveitis (AAU). Flow cytometric analysis was performed on the lymphocyte subsets from the AH and peripheral blood (PB) samples during the active phase of intraocular inflammation. Five inflammatory cytokines were measured in each AH sample and various clinical characteristics were also assessed. Results VZV deoxyribonucleic acid (DNA) was detected by real-time polymerase chain reaction (PCR) in AH from all the ARN patients, who showed higher CD8+ T lymphocytes population in AH than the AAU patients (p = 0.006). CD4/CD8 ratios of T lymphocytes and the percentage of CD8 + CD25+ T lymphocytes in AH were significantly lower in ARN than in AAU (p = 0.006; p = 0.012). In the ARN patients, the percentages of CD4+ and CD8+ T lymphocytes in AH were higher than those found in PB. The percentage of CD4 + CD25+ T lymphocytes in AH was significantly higher than the proportion in PB in the AAU patients (p = 0.001). Immunoregulatory cytokine Interleukin-10 in AH was significantly elevated in the ARN patients in comparison with the case of the AAU patients (p = 0.036). In ARN, the copy number of VZV DNA in AH positively correlated with the percentage of CD8+ T lymphocytes in AH and negatively correlated with the CD4/CD8 ratio in AH during the course of disease treatment (p = 0.009, r = 0.92; p = 0.039, r = − 0.834). Conclusion The ARN patients caused by VZV had different intraocular T lymphocyte subsets and cytokines profile than those of the non-infectious patients. High percentages of CD8+ T lymphocytes and low CD4/CD8 T cell ratios may be a potential biomarker for diagnosis of viral-infectious uveitis. T lymphocytes examination at the inflammatory sites has the potential to become a useful research tool for differentiating viral and non-viral uveitis.


2020 ◽  
Author(s):  
Hao Kang ◽  
Yunbo Wei ◽  
Ming Liu ◽  
Di Yu ◽  
Yong Tao

Abstract Background: The purpose of this study is to investigate the aqueous humor (AH) T lymphocyte subsets and cytokines of acute retinal necrosis (ARN) to elucidate the immunologic inflammatory features of this disorder.Methods: Three patients with ARN infected with varicella zoster virus (VZV) who underwent multiple intravitreal injections of ganciclovir were enrolled in this study. The control group consisted of four non-viral infectious patients with acute anterior uveitis (AAU). Flow cytometric analysis was performed on the lymphocyte subsets from the AH and peripheral blood (PB) samples during the active phase of intraocular inflammation. Five inflammatory cytokines were measured in each AH sample and various clinical characteristics were also assessed.Results: VZV DNA was detected by real-time polymerase chain reaction (PCR) in AH from all the ARN patients, who showed higher CD8+ T lymphocytes population in AH than the AAU patients (p=0.006). CD4/CD8 ratios of T lymphocytes and the percentage of CD8+CD25+ T lymphocytes in AH were significantly lower in ARN than in AAU (p=0.006; p=0.012). In the ARN patients, the percentages of CD4+ and CD8+ T lymphocytes in AH were higher than those found in PB. The percentage of CD4+CD25+ T lymphocytes in AH was significantly higher than the proportion in PB in the AAU patients (p=0.001). Immunoregulatory cytokine Interleukin-10 in AH was significantly elevated in the ARN patients in comparison with the case of the AAU patients (p=0.036). In ARN, the copy number of VZV DNA in AH positively correlated with the percentage of CD8+ T lymphocytes in AH and negatively correlated with the CD4/CD8 ratio in AH during the course of disease treatment (p=0.009, r=0.92; p=0.039, r=-0.834).Conclusion: The ARN patients caused by VZV had different intraocular T lymphocyte subsets and cytokines profile than those of the non-viral infectious patients. High percentages of CD8+ T lymphocytes and low CD4/CD8 T cell ratios may be a potential biomarker for diagnosis of viral-infectious uveitis. T lymphocytes examination at the inflammatory sites has the potential to become a useful research tool for differentiating viral and non-viral uveitis.


2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 626-626
Author(s):  
Jose M Vieitez ◽  
Marco Moro-Garcia ◽  
Paula Jiménez-Fonseca ◽  
Carlos A Echeverria de ◽  
Mar Iglesias Escudero ◽  
...  

626 Background: CRC patients treated with anti-EGFR having skin reactions tend to have a better outcome regardless of the presence of mutations in the RAS. This fact, repeated with various antibodies makes us think that the basal immunology, or its ability to react to these proteins is actually responsible for this phenomenon. We initiated an exploratory study to identify which parameters/immunological pathways might be related to skin reactions. Methods: Seric levels of immunoglobulins (IgG, IgA, and IgM) and complement factors (c3 and c4) were measured. Leukocyte and lymphocyte subsets were also quantified in peripheral blood. We evaluated cytotoxic activity of NK lymphocytes (CD107a expression in response to K562 cells) and activation of CD4+ and CD8+ T-lymphocytes in response to anti-CD3 stimulation (expression of CD38, HLA-DR, CD25 and CD69). Results: 17 consecutive patients were included from 29/08/2012 to 17/11/14. Median age was 66 (range 50-80), median number of organ affected 1 (range 1-3), liver affected in 8 patients. 9 Patients were treated with folfiri/panitumumab, 4 cpt11/panitumumab, 4 with panitumumab monochemotherapy. Two patients presented a partial response, median days to progression were 176 days (range 15-652). Levels of immunoglobulins, complement factors, and leukocyte subsets showed no differences between both groups of patients (with or without skin reactions). Increased T-lymphocyte percentages were found in patients without skin reactions, mainly explained by higher levels of CD8+ T-lymphocytes but with a more differentiated phenotype. Neither frequencies nor cytotoxic activity of NK-lymphocytes showed differences between patients. However, anti-CD3 stimulation induced higher activation status in CD4+ and CD8+ T-lymphocytes in patients having skin reactions, with increased levels of activation marker expression of CD38, HLA-DR, CD25 and mainly CD69. Conclusions: T-lymphocytes of CRC-patients having skin reaction in response to anti-EGFR treatment seem to have a less differentiated status and a higher ability to be activated by anti-CD3 stimulation in vitro.


2018 ◽  
Vol 140 (1) ◽  
pp. 60-66 ◽  
Author(s):  
Yang Chen ◽  
Yanyan Xie ◽  
Min Ruan ◽  
Jinning Shi

Objective: The aim of this work was to investigate the influence of T lymphocyte subsets and platelet-specific autoantibodies on immune thrombocytopenia (ITP) with dexamethasone therapy. Methods: The samples were obtained from patients before therapy. T lymphocyte subsets were measured by flow cytometry, and platelet-specific autoantibodies were evaluated by modified monoclonal antibody immobilization of platelet antigen assay. Results: A total of 50 ITP patients were involved in the study. Twenty-three were anti-GPIbα antibody positive and were treated with dexamethasone, with a response rate of 47.8%. Twenty-seven cases were anti-GPIbα antibody negative, with a response rate of 77.8%. A significant difference was detected (p < 0.05). The level of CD4+ T lymphocytes in ITP patients was lower compared with the control group (p < 0.05). The level of CD8+ T lymphocytes was higher than that in the normal controls (p < 0.05). Additionally, the patients with a higher level of CD8+ T lymphocytes and lower level of CD4+ T lymphocytes were more likely to respond to dexamethasone treatment. Moreover, we observed that ITP patients associated with anti-GPIIb/IIIa antibodies had lower levels of CD4+ T lymphocytes and higher CD8+ T lymphocyte levels. Conclusions: There was insensitivity to dexamethasone treatment in ITP patients who were anti-GPIbα antibody positive. The detection of T lymphocyte subsets is useful in ITP patients for forecasting the outcome of dexamethasone treatment. There were some relationships between the different antibodies and the levels of T lymphocyte subsets.


Cytotherapy ◽  
2013 ◽  
Vol 15 (4) ◽  
pp. S37
Author(s):  
K. Ruhnke ◽  
A. Foerster-Marniok ◽  
V. Traska ◽  
J. Stuth ◽  
M. Essl ◽  
...  

1995 ◽  
Vol 23 (01) ◽  
pp. 27-36 ◽  
Author(s):  
Hoon Ryu ◽  
Chang Duk Jun ◽  
Bok Soo Lee ◽  
Byung Min Choi ◽  
Hyung Min Kim ◽  
...  

The effect of Qigong training on proportions of T lymphocyte subsets was investigated in human peripheral blood. We observed that the ratio of CD4+/CD8+ T lymphocytes was increased as much as 50% in a trainee group who practiced Qigong training more than 5 months compared to a normal healthy group who did not practice. The absolute number of CD4+ T lymphocytes was also elevated in trainee group with 100 cells/mm 3 more than in normal healthy group. The positive correlation between the ratio of CD4+/CD8+ T lymphocytes and the ratio of CD4+45RA-/CD4+ CD45RA+ T lymphocytes was shown in the trainee group. In contrast, there was a negative correlation between the ratio of CD4+/CD8+ T lymphocytes and the ratio of CD8+CD57+/CD8+CD57- T lymphocytes in the trainee group. The data indicate that Qigong training affects the profile of lymphocyte subsets in human peripheral blood, especially the proportion of CD4+ T lymphocytes.


Blood ◽  
2004 ◽  
Vol 104 (9) ◽  
pp. 2840-2848 ◽  
Author(s):  
William J. Grossman ◽  
James W. Verbsky ◽  
Benjamin L. Tollefsen ◽  
Claudia Kemper ◽  
John P. Atkinson ◽  
...  

Abstract Cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells use the perforin/granzyme pathway as a major mechanism to kill pathogen-containing cells and tumor cells.1,2 Dysregulation of this pathway results in several human diseases, such as hemophagocytic lymphohistiocytosis. Here we characterize the single-cell expression pattern of granzymes A and B in human lymphocytes using a flow cytometry-based assay. We demonstrate that most circulating CD56+8- NK cells, and approximately half of circulating CD8+ T lymphocytes, coexpressed both granzymes A and B. In contrast, few circulating CD4+ T lymphocytes expressed granzymes A or B. Activation of CD8+ T lymphocytes with concanavalin A (ConA)/interleukin-2 (IL-2), and activation of CD4+ T lymphocytes with antibodies to CD3/CD28 or CD3/CD46 (to generate T regulatory [Tr1] cells), induced substantial expression of granzyme B, but not granzyme A. Naive CD4+CD45RA+ cells stimulated with antibodies to CD3/CD46 strongly expressed granzyme B, while CD3/CD28 stimulation was ineffective. Finally, we show that granzyme B-expressing CD4+ Tr1 cells are capable of killing target cells in a perforin-dependent, but major histocompatibility complex (MHC)/T-cell receptor (TCR)-independent, manner. Our results demonstrate discordant expression of granzymes A and B in human lymphocyte subsets and T regulatory cells, which suggests that different granzymes may play unique roles in immune system responses and regulation.


2021 ◽  
Vol 12 ◽  
Author(s):  
Qin Wang ◽  
Shangbiao Li ◽  
Simiao Qiao ◽  
Zhihao Zheng ◽  
Xiaotong Duan ◽  
...  

PurposeRadiation therapy (RT) induces an immune response, but the relationship of this response with tumor type is not fully understood. This meta-analysis further elucidated this relationship by analyzing the changes in T lymphocyte subsets in different tumors before and after radiotherapy.MethodsWe searched English-language electronic databases including PubMed, EMBASE, and the Cochrane Library to collect studies on the changes in peripheral blood CD3+ T lymphocytes, CD4+ T lymphocytes, and CD8+ T lymphocytes before and after radiotherapy in tumor patients from January 2015 to April 2021. The quality of the included literature was evaluated using the NOS scale provided by the Cochrane Collaboration, and statistical software RevMan 5.4 was used to analyze the included literature. P&lt;0.05 was considered to indicate statistical significance.ResultsA total of 19 studies in 16 articles involving 877 tumor patients were included. All data were collected within 1 month before or after radiotherapy. Meta-analysis showed that numbers of CD3+ T lymphocytes (SMD: -0.40; 95% CI [-0.75, -0.04]; p = 0.03) and CD4+ T lymphocytes (SMD: -0.43; 95% CI: [-0.85, -0.02]; p = 0.04) were significantly reduced after radiotherapy compared with before treatment, but there was no statistically significant difference for CD8+ T lymphocytes (SMD: 0.33; 95% CI: [-0.88, 0.74]; p = 0.12). Subgroup analysis showed that peripheral blood T lymphocytes decreased in head and neck cancer. However, in prostate cancer and breast cancer, there was no significant change in peripheral blood. 1 month after radiotherapy, it has a potential proliferation and activation effect on lymphocytes in esophageal cancer and lung cancer. The results showed that CD8+T lymphocytes increased in peripheral blood after SBRT. Radiotherapy alone reduced CD3+ T lymphocyte numbers.ConclusionsWithin 1 month of radiotherapy, patients have obvious immunological changes, which can cause apoptosis and reduction of T lymphocytes, and affect the balance of peripheral blood immune cells. The degree of immune response induced by radiotherapy differed between tumor types.


Blood ◽  
1998 ◽  
Vol 92 (1) ◽  
pp. 198-206 ◽  
Author(s):  
Jörn E. Schmitz ◽  
Meryl A. Forman ◽  
Michelle A. Lifton ◽  
Orlando Concepción ◽  
Keith A. Reimann ◽  
...  

CD8+ T lymphocytes play a pivotal role in controlling human immunodeficiency virus (HIV)-1 replication in vivo. We have performed four-color flow cytometric analysis of CD8+peripheral blood lymphocytes (PBL) from 21 HIV-1 seronegative and 103 seropositive individuals to explore the phenotypic heterogeneity of CD8β-chain expression on CD8+ T lymphocytes and to clarify how its expression on CD8+ T lymphocytes may relate to acquired immunodeficiency syndrome (AIDS) clinical progression. We showed that the single monoclonal antibody (MoAb) 2ST8-5H7, directed against the CD8αβ-heterodimer, identifies CD8+ T lymphocytes as effectively as the conventional combination of anti-CD3 and anti-CD8α antibodies. However, we detected a significantly lower mean fluorescence (MF) of anti-CD8αβ staining on PBL from HIV-1 seropositive donors as compared with seronegative donors. In fact, CD8+ T lymphocytes from HIV-1–infected individuals with the lowest CD4 counts showed the lowest levels of CD8αβ MF. To explore further this change in CD8αβ expression, we assessed the expression of 14 different cell surface molecules on CD8αβ+ T lymphocytes of PBL from 11 HIV-1 seronegative and 22 HIV-1 seropositive individuals. The MF of anti-CD8αβ staining was significantly reduced on CD8+T lymphocyte subsets that showed immunophenotypic evidence of activation. The subset of lymphocytes expressing low levels of CD8αβ expressed higher levels of activation, adhesion, and cytotoxic-associated molecules and was predominantly CD45RO+ and CD28−. Finally, we monitored the expression of the CD8αβ-heterodimer on PBL of eight HIV-1–infected individuals over a 16-week period after the initiation of highly active antiretroviral therapy (HAART), including zidovudine (ZDV), lamivudine (3TC), and indinavir (IDV), and found a significant increase in the expression of the CD8αβ-heterodimer. These results suggest that antibodies recognizing the CD8αβ-heterodimer are useful tools to specifically identify CD8+ T lymphocytes. Moreover, the quantitative monitoring of CD8αβ expression allows the detection of discrete CD8+ T lymphocyte subsets and may be useful for assessing the immune status of individuals infected with HIV-1.


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