High Expression of the Ectonucleotidase CD39 on T Cells from the Inflamed Site Identifies Two Distinct Populations, One Regulatory and One Memory T Cell Population

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.

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Characterization of a subset of CD4+ T cells expressing CD161 in cancer patients and healthy individuals

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.20016 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 20016-20016

Author(s):

E. G. Iliopoulou ◽

M. V. Karamouzis ◽

S. A. Perez ◽

A. Ardavanis ◽

C. N. Baxevanis ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Cancer Patients ◽

Cell Population ◽

Peripheral Blood ◽

Th2 Cytokines ◽

Healthy Individuals ◽

Memory T Cell ◽

Th1 And Th2 Cytokines ◽

Th1 And Th2

20016 Background: CD161 is a glycoprotein expressed in >90% of NK and 25% of T cells in the peripheral blood of healthy individuals. Several NK receptors on T cells infiltrating tumors have been proven to negatively influence their effector function and therefore play a role in tumor escape. In this study, we investigated T cells expressing CD161 in the peripheral blood mononuclear cells (PBMC), tumor infiltrarting lymphocytes (TIL) or malignant effusions (ME) from patients with several types of cancer. Methods: Expression of CD161 in CD4+ or CD8+ (lacking CD56) T cells, was examined using four-colour flow cytometry. The proliferative capacity and potential cytokine production of purified CD4+CD161+CD56− cells, were studied after weak or strong stimulation, with or without costimulation, in the presence or absence of Interleukin-2 (IL-2). The possible regulatory function of activated CD4+CD161+CD56− cells on T cell allo-responses was also investigated. Results: CD4+CD161+CD56− T cells were significantly increased (P < 0.01) in TIL, either from tumor tissue (n = 8) or metastatic lymph nodes (n = 5), and ME (n = 25), compared to PBMC from both cancer patients (n = 36) and healthy individuals (n = 12). CD4+CD161+CD56− cells from all sources tested, have the same phenotypic characteristics: they comprise a memory T cell population (CD45RO+CD45RA−) expressing high CD28 and CD95 and low CD25, CD38 and HLA-DR. Co-stimulation via CD28 is important for induction of proliferation and production of large amounts of Th1 and Th2 cytokines (IFN-γ, TNF-a, GM-CSF, IL-4 and IL-10). Following co-stimulation, CD4+CD161+CD56− cells also exert a suppressive activity on autologous PBMC allo-responses. The latter effect does not require cell-to-cell contact and is mediated by soluble factors, including IL10, since neutralization of IL10 partially restored the immune response. Conclusions: CD4+CD161+CD56− cells represent a distinct memory T cell population that is significantly increased in TIL and ME in patients with cancer. These cells are capable of secreting large amounts of both Th1 and Th2 cytokines and might play an immunosuppressive role, mainly through IL-10 production, depending on the microenvironment in which they develop. No significant financial relationships to disclose.

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CD28nullCD4+ T Cells - Characterization of an Effector Memory T-Cell Population in Patients with Rheumatoid Arthritis

Scandinavian Journal of Immunology ◽

10.1111/j.0300-9475.2004.01464.x ◽

2004 ◽

Vol 60 (1-2) ◽

pp. 199-208 ◽

Cited By ~ 52

Author(s):

A. E. R. Fasth ◽

D. Cao ◽

R. van Vollenhoven ◽

C. Trollmo ◽

V. Malmstrom

Keyword(s):

Rheumatoid Arthritis ◽

T Cells ◽

T Cell ◽

Cell Population ◽

Effector Memory ◽

Memory T Cell

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Circulating CD4+ memory T cells give rise to a CD69+ resident memory T cell population in non-inflamed human skin

10.1101/490094 ◽

2018 ◽

Cited By ~ 2

Author(s):

Maria M Klicznik ◽

Ariane Benedetti ◽

Angelika Stoecklinger ◽

Daniel J Campbell ◽

Iris K Gratz

Keyword(s):

T Cells ◽

Candida Albicans ◽

T Cell ◽

Human Skin ◽

Cell Population ◽

Memory T Cells ◽

Humanized Mouse Model ◽

Normal Human Skin ◽

Memory T Cell ◽

Resident Memory T Cells

The blood of human adults contains a pool of circulating CD4+ memory T cells and normal human skin contains a CD4+CD69+ memory T cell population that produce IL17 in response to Candida albicans. Here we studied the generation of CD4+CD69+ memory T cells in human skin from a pool of circulating CD4+ memory T cells. Using adoptive transfer of human PBMC into a skin-humanized mouse model we discovered the generation of CD4+CD69+ resident memory T cells in human skin in absence of infection or inflammation. These CD4+CD69+ resident memory T cells were activated and displayed heightened effector function in response to Candida albicans. These studies demonstrate that a CD4+CD69+ T cell population can be established in human skin from a pool of circulating CD4+ memory T cells in absence of infection/inflammation. The described process might be a novel way to spread antigen-specific immunity at large barrier sites even in absence of infection or inflammation.

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Transforming growth factor-β signaling is constantly shaping memory T-cell population

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1510119112 ◽

2015 ◽

Vol 112 (35) ◽

pp. 11013-11017 ◽

Cited By ~ 27

Author(s):

Chaoyu Ma ◽

Nu Zhang

Keyword(s):

T Cells ◽

T Cell ◽

Growth Factor ◽

Cell Population ◽

Transforming Growth Factor ◽

Memory T Cells ◽

Transforming Growth Factor Β ◽

Memory T Cell

The long-term maintenance of memory T cells is essential for successful vaccines. Both the quantity and the quality of the memory T-cell population must be maintained. The signals that control the maintenance of memory T cells remain incompletely identified. Here we used two genetic models to show that continuous transforming growth factor-β signaling to antigen-specific T cells is required for the differentiation and maintenance of memory CD8+ T cells. In addition, both infection-induced and microbiota-induced inflammation impact the phenotypic and functional identity of memory CD8+ T cells.

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Multicytokine and Polyfunctional CMV-Specific T Cells Are Associated with Stem Cell Transplant Donor CMV Serostatus.

Blood ◽

10.1182/blood.v110.11.4992.4992 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4992-4992

Author(s):

Wendi Zhou ◽

Jeffrey Longmate ◽

Joycelynne Palmer ◽

Simon F. Lacey ◽

Ghislaine A. Hawkins ◽

...

Keyword(s):

T Cells ◽

Stem Cell ◽

T Cell ◽

Cell Population ◽

Cd8 T Cells ◽

Memory T Cell ◽

Tnf Α ◽

Ifn Γ ◽

Cmv Reactivation ◽

Cmv Status

Abstract Recently, a phenotype of CD8+ T cells was discovered that distinguishes long-term non-progressors from rapid progressors in HIV infection. The phenotype consists of a combination of cytokines and the CD107 surface marker, associated with competence for cytotoxicity, all expressed from the same CD8+ T cell. Our published work highlighted a significant difference in frequency of IFN-γ and TNF-α double cytokine expressing T cells, which are more frequently associated with CMV-positive than negative donors of stem cell transplants (HCT). Both clinical and basic studies have shown that TNF-α expression is associated with mature immunity, and its proper regulation is associated with a favorable outcome of HCT. We investigated the quality of T cell immunity targeting the CMV-pp65 antigen in a longitudinal study of HCT recipients up to 1 year post-Tx. HCT recipients with both CMV-positive and negative donors were accrued, and differences were compared between the two cohorts based on single and multi-cytokine expression (IFN-γ, MIP1-β, TNF-α) and the cytotoxicity marker, CD107. We tested whether the length of time these phenotypic immune differences persisted in the HCT recipient was associated with donor CMV status. A total of 61 donor-recipient pairs were compared. Using an ex vivo approach, multiparameter flow cytometry was used to obtain percentages for each individual T cell cytokine producing population, as well as comparisons between populations after CMV-pp65 full-length peptide library stimulation. We present results at 90–360d post-HCT. Comparisons of levels of multi-functional (4 parameter) T cells showed significant differences from CMV-positive and negative donors reflecting an increased frequency of 4-function T cells between 90–360d post-Tx. These levels were statistically significant (p<0.01) between the groups (student T-test). In contrast, removal of TNF-α from the panel resulted in the elimination of the difference between the 2 cohorts. The strong association of CMV status with inclusion of TNF-α, a maturation marker in the multi-cytokine phenotype, forecasts the key role of the memory T cell phenotype in the early development of protective immunity in the HCT recipient. Similar to the case in HIV progression studies, the preponderance of multifunctional (3 or 4 function) CD8+ T cells were found in recipients with CMV-positive donors versus those with CMV-negative donors, who were biased towards the double or single cytokine function phenotype between 90–360d post-HCT. The direct impact focuses on memory development, while insight on the relationship of these T cell populations to the frequency of CMV reactivation, infection, and overall survival were also investigated. Comparing HCT recipients who had CMV reactivation from those who did not, as well as stratification by donor CMV status clearly shows the greater frequency of the memory T cell population in recipients with CMV-positive donors. CMV reactivation contributes to the development of a CMV-specific T cell population that is intermediate between the low levels of those with no reactivation and a CMV-negative donor, versus having a CMV-positive donor. This data also reflects the influence of prior memory status in contributing to the more rapid development of a mature CMV-specific T cell population in the HCT recipient.

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Faculty Opinions recommendation of CCR6 is expressed on an IL-10-producing, autoreactive memory T cell population with context-dependent regulatory function.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.3140956.2828054 ◽

2010 ◽

Author(s):

George Yap

Keyword(s):

T Cell ◽

Cell Population ◽

Regulatory Function ◽

Memory T Cell ◽

Context Dependent

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Detection of IFNγ-Secreting CD4+ and CD8+ Memory T Cells in COVID-19 Convalescents after Stimulation of Peripheral Blood Mononuclear Cells with Live SARS-CoV-2

Viruses ◽

10.3390/v13081490 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1490

Author(s):

Victoria Matyushenko ◽

Irina Isakova-Sivak ◽

Igor Kudryavtsev ◽

Arina Goshina ◽

Anna Chistyakova ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Memory T Cells ◽

Natural Infection ◽

Intracellular Cytokine Staining ◽

T Cell Responses ◽

Effector Memory ◽

Memory T Cell ◽

Cell Responses ◽

Stimulation Of

Background: New coronavirus SARS-CoV-2, a causative agent of the COVID-19 pandemic, has been circulating among humans since November 2019. Multiple studies have assessed the qualitative and quantitative characteristics of virus-specific immunity in COVID-19 convalescents, however, some aspects of the development of memory T-cell responses after natural SARS-CoV-2 infection remain uncovered. Methods: In most of published studies T-cell immunity to the new coronavirus is assessed using peptides corresponding to SARS-CoV-1 or SARS-CoV-2 T-cell epitopes, or with peptide pools covering various parts of the viral proteins. Here, we determined the level of CD4+ and CD8+ memory T-cell responses in COVID-19 convalescents by stimulating PBMCs collected 1 to 6 months after recovery with sucrose gradient-purified live SARS-CoV-2. IFNγ production by the central and effector memory helper and cytotoxic T cells was assessed by intracellular cytokine staining assay and flow cytometry. Results: Stimulation of PBMCs with live SARS-CoV-2 revealed IFNγ-producing T-helper effector memory cells with CD4+CD45RA−CCR7− phenotype, which persisted in circulation for up to 6 month after COVID-19. In contrast, SARS-CoV-2-specific IFNγ-secreting cytotoxic effector memory T cells were found at significant levels only shortly after the disease, but rapidly decreased over time. Conclusion: The stimulation of immune cells with live SARS-CoV-2 revealed a rapid decline in the pool of effector memory CD8+, but not CD4+, T cells after recovery from COVID-19. These data provide additional information on the development and persistence of cellular immune responses after natural infection, and can inform further development of T cell-based SARS-CoV-2 vaccines.

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Key Markers Involved in the Anticolon Cancer Response of CD8+ T Cells through the Regulation of Cholesterol Metabolism

Journal of Oncology ◽

10.1155/2021/9398661 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Liang Dong ◽

Xi Yang ◽

Yangyanqiu Wang ◽

Yin Jin ◽

Qing Zhou ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Network Analysis ◽

Gene Family ◽

Cd8 T Cells ◽

Cholesterol Metabolism ◽

Differential Expression Analysis ◽

High Expression ◽

Ppi Network ◽

Low Expression

Background. T cell-mediated antitumor immune response is the basis of colorectal cancer (CRC) immunotherapy. Cholesterol plays an important role in T cell signal transduction and function. Apolipoprotein E (APOE) plays a major role in cholesterol metabolism. Objective. To screen and analyze key markers involved in the anticolon cancer response of CD8+ T cells through the regulation of cholesterol metabolism. Methods. Based on the median cutoff of the expression value of APOE according to the data downloaded from The Cancer Genome Atlas and Gene Expression Omnibus database, patients were grouped into low and high expression groups. Differences in clinical factors were assessed, and survival analysis was performed. Differentially expressed genes (DEGs) in the high and low expression groups were screened, followed by the analysis of differences in tumor-infiltrating immune cells and weighted gene coexpression network analysis results. The closely related genes to APOE were identified, followed by enrichment analysis, protein–protein interaction (PPI) network analysis, and differential expression analysis. Immunohistochemical staining (IHC) was used to detect the expression of CD8 in CRC tissues. Results. There were significant differences in prognosis and pathologic_N between the APOE low and high expression groups. A total of 2,349 DEGs between the high and low expression groups were selected. A total of 967 genes were obtained from the blue and brown modules. The probability of distribution of CD8+ T cells differed significantly between the two groups, and 320 closely related DEGs of APOE were screened. Genes including the HLA gene family, B2M, IRF4, and STAT5A had a higher degree in the PPI network. GEO datasets verified the prognosis and the related DEGs of APOE. IHC staining verified the relationship between the distribution of CD8+ T cells and APOE expression. Conclusion. Genes including the HLA gene family, B2M, IRF4, and STAT5A might be the key genes involved in the anticolon cancer response of CD8+ T cells through the regulation of cholesterol metabolism.

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