scholarly journals CD4+ virtual memory: Antigen-inexperienced T cells reside in the naïve, regulatory, and memory T cell compartments at similar frequencies, implications for autoimmunity

2017 ◽  
Vol 77 ◽  
pp. 76-88 ◽  
Author(s):  
Alina I. Marusina ◽  
Yoko Ono ◽  
Alexander A. Merleev ◽  
Michiko Shimoda ◽  
Hiromi Ogawa ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Virtual Memory ◽  
Memory T Cell ◽  
Cell Compartments

scholarly journals 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 ◽  
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.

scholarly journals Naïve Regulatory T Cell Subset Is Altered in X-Linked Agammaglobulinemia

2021 ◽  
Vol 12 ◽  
Author(s):  
Pavel V. Shelyakin ◽  
Ksenia R. Lupyr ◽  
Evgeny S. Egorov ◽  
Ilya A. Kofiadi ◽  
Dmitriy B. Staroverov ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cell ◽  
Cell Subset ◽  
Cell Receptor ◽  
T Cell Subsets ◽  
Cell Compartments ◽  
Expression Of Genes ◽  
Tcr Repertoire ◽  
Antigen Presenting

The interplay between T- and B-cell compartments during naïve, effector and memory T cell maturation is critical for a balanced immune response. Primary B-cell immunodeficiency arising from X-linked agammaglobulinemia (XLA) offers a model to explore B cell impact on T cell subsets, starting from the thymic selection. Here we investigated characteristics of naïve and effector T cell subsets in XLA patients, revealing prominent alterations in the corresponding T-cell receptor (TCR) repertoires. We observed immunosenescence in terms of decreased diversity of naïve CD4+ and CD8+ TCR repertoires in XLA donors. The most substantial alterations were found within naïve CD4+ subsets, and we have investigated these in greater detail. In particular, increased clonality and convergence, along with shorter CDR3 regions, suggested narrower focused antigen-specific maturation of thymus-derived naïve Treg (CD4+CD45RA+CD27+CD25+) in the absence of B cells - normally presenting diverse self and commensal antigens. The naïve Treg proportion among naïve CD4 T cells was decreased in XLA patients, supporting the concept of impaired thymic naïve Treg selection. Furthermore, the naïve Treg subset showed prominent differences at the transcriptome level, including increased expression of genes specific for antigen-presenting and myeloid cells. Altogether, our findings suggest active B cell involvement in CD4 T cell subsets maturation, including B cell-dependent expansion of the naïve Treg TCR repertoire that enables better control of self-reactive T cells.

scholarly journals TIM-3 Engagement Promotes Effector Memory T Cell Differentiation of Human Antigen-Specific CD8 T Cells by Activating mTORC1

2017 ◽  
Vol 199 (12) ◽  
pp. 4091-4102 ◽  
Author(s):  
Nina Chi Sabins ◽  
Olesya Chornoguz ◽  
Karen Leander ◽  
Fred Kaplan ◽  
Richard Carter ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Differentiation ◽  
T Cell ◽  
Cd8 T Cells ◽  
T Cell Differentiation ◽  
Effector Memory ◽  
Memory T Cell

scholarly journals T cell and non-T cell compartments can independently determine resistance to Leishmania major.

1995 ◽  
Vol 181 (3) ◽  
pp. 845-855 ◽  
Author(s):  
A H Shankar ◽  
R G Titus
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Leishmania Major ◽  
Cell Receptor ◽  
Disease Outcome ◽  
Chimeric Mice ◽  
Antigen Specificity ◽  
Ifn Gamma ◽  
Cell Compartments

In experimental murine cutaneous leishmaniasis caused by Leishmania major (Lm), the cellular determinants governing development of protective or exacerbative T cells are not well understood. We, therefore, attempted to determine the influence of T cell and non-T cell compartments on disease outcome. To this end, T cell chimeric mice were constructed using adult thymectomized lethally irradiated, bone marrow-reconstituted (ATXBM) animals of genetically resistant, C57BL/6, or susceptible, BALB/c, backgrounds. These hosts were engrafted with naive T cell populations from H-2-congenic susceptible, BALB.B6-H-2b, or resistant, C57BL/6.C-H-2d, animals, respectively. Chimeric mice were then infected with Lm, and disease outcome was monitored. BALB/c T cell chimeric mice, BALB/c ATXBM hosts given naive C57BL/6.C-H-2d T cells, resolved their infections as indicated by reductions in both lesion size and parasite numbers. Furthermore, the mice developed typical Th1 (interferon[IFN]-gamma hiinterleukin[IL]-4lo) cytokine patterns. In contrast, both sham chimeric, BALB/c ATXBM hosts given naive BALB/c T cells, and control irradiated euthymic mice succumbed to infection, producing Th2 profiles (IFN-gamma loIL-4hiIL-10hi). C57BL/6 T cell chimeras, C57BL/6 ATXBM hosts given naive BALB.B6-H-2b T cells, resolved their infections as did C57BL/6 sham chimeras and euthymic controls. Interestingly, whereas C57BL/6 control animals produced Th1 cytokines, chimeric animals progressed from Th0 (IFN-gamma hiIL-4hiIL-10hi) to Th2 (IFN-gamma loIL-4hiIL-10hi) cytokine profiles as cure ensued. Both reconstitution and chimeric status of all mice were confirmed by flow cytometry. In addition, T cell receptor V beta usage of Lm-specific blasts was determined. In all cases, V beta use was multiclonal, involving primarily V beta 2, 4, 6, 8.1, 8.2, 8.3, 10, and 14, with relative V beta frequencies differing between H-2b and H-2d animals. Most importantly, however, these differences did not segregate between cure and noncure outcomes. These findings indicate that: (a) genetic traits determining cure in Lm infection can direct disease outcome from both T cell and non-T cell compartments; (b) the presence of the curing genotype in only one compartment is sufficient to confer cure; (c) curing genotype T cells autonomously assume a Th1 cytokine profile-mediating cure; (d) noncuring genotype T cells can mediate cure in a curing environment, despite the onset of Th2 cytokine production; and lastly, (e) antigen specificity of responding T cells, as assessed by V beta T cell receptor diversity, is not a critical determinant of disease outcome.

scholarly journals Frontline Science: Late CD27 stimulation promotes IL‐7Rα transcriptional re‐expression and memory T cell qualities in effector CD8 + T cells

2019 ◽  
Vol 106 (5) ◽  
pp. 1007-1019 ◽  
Author(s):  
Han Dong ◽  
Andrew Buckner ◽  
Jessica Prince ◽  
Timothy Bullock
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Memory T Cell

scholarly journals Cytotoxic Activity and Memory T Cell Subset Distribution of in vitro-Stimulated CD8+ T Cells Specific for HER2/neu Epitopes

2019 ◽  
Vol 10 ◽  
Author(s):  
Maria Kuznetsova ◽  
Julia Lopatnikova ◽  
Julia Shevchenko ◽  
Alexander Silkov ◽  
Amir Maksyutov ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cytotoxic Activity ◽  
Cd8 T Cells ◽  
Cell Subset ◽  
T Cell Subset ◽  
Memory T Cell ◽  
Subset Distribution

scholarly journals Impact of multiple hits with cognate antigen on memory CD8+ T-cell fate

2020 ◽  
Vol 32 (9) ◽  
pp. 571-581 ◽  
Author(s):  
Shiki Takamura
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Memory T Cells ◽  
Cd8 T Cell ◽  
T Cell Subsets ◽  
Primary Immune Response ◽  
Memory T Cell ◽  
Cognate Antigen ◽  
Memory Cd8 T Cell

Abstract Antigen-driven activation of CD8+ T cells results in the development of a robust anti-pathogen response and ultimately leads to the establishment of long-lived memory T cells. During the primary response, CD8+ T cells interact multiple times with cognate antigen on distinct types of antigen-presenting cells. The timing, location and context of these antigen encounters significantly impact the differentiation programs initiated in the cells. Moderate re-activation in the periphery promotes the establishment of the tissue-resident memory T cells that serve as sentinels at the portal of pathogen entry. Under some circumstances, moderate re-activation of T cells in the periphery can result in the excessive expansion and accumulation of circulatory memory T cells, a process called memory inflation. In contrast, excessive re-activation stimuli generally impede conventional T-cell differentiation programs and can result in T-cell exhaustion. However, these conditions can also elicit a small population of exhausted T cells with a memory-like signature and self-renewal capability that are capable of responding to immunotherapy, and restoration of functional activity. Although it is clear that antigen re-encounter during the primary immune response has a significant impact on memory T-cell development, we still do not understand the molecular details that drive these fate decisions. Here, we review our understanding of how antigen encounters and re-activation events impact the array of memory CD8+ T-cell subsets subsequently generated. Identification of the molecular programs that drive memory T-cell generation will advance the development of new vaccine strategies that elicit high-quality CD8+ T-cell memory.

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