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Expression of IL-7R? and KLRG1 defines functionally distinct CD8+ T-cell populations in humans.

ABSTRACT: During acute viral infections in mice, IL-7R? and KLRG1 together are used to distinguish the short-lived effector cells (SLEC; IL-7R?lo KLRGhi ) from the precursors of persisting memory cells (MPEC; IL-7R?hi KLRG1lo ). We here show that these markers can be used to define distinct subsets in the circulation and lymph nodes during the acute phase and in "steady state" in humans. In contrast to the T cells in the circulation, T cells derived from lymph nodes hardly contain any KLRG1-expressing cells. The four populations defined by IL-7R? and KLRG1 differ markedly in transcription factor, granzyme and chemokine receptor expression. When studying renal transplant recipients experiencing a primary hCMV and EBV infection, we also found that after viral control, during latency, Ki-67-negative SLEC can be found in the peripheral blood in considerable numbers. Thus, combined analyses of IL-7R? and KLRG1 expression on human herpes virus-specific CD8+ T cells can be used to separate functionally distinct subsets in humans. As a noncycling IL-7R?lo KLRG1hi population is abundant in healthy humans, we conclude that this combination of markers not only defines short-lived effector cells during the acute response but also stable effector cells that are formed and remain present during latent herpes infections.

SUBMITTER: Remmerswaal EBM

PROVIDER: S-EPMC6593687 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Expression of IL-7Rα and KLRG1 defines functionally distinct CD8+ T-cell populations in humans.

Remmerswaal Ester B M EBM Hombrink Pleun P Nota Benjamin B Pircher Hanspeter H Ten Berge Ineke J M IJM van Lier René A W RAW van Aalderen Michiel C MC

European journal of immunology 20190325 5

During acute viral infections in mice, IL-7Rα and KLRG1 together are used to distinguish the short-lived effector cells (SLEC; IL-7Rαlo KLRGhi ) from the precursors of persisting memory cells (MPEC; IL-7Rαhi KLRG1lo ). We here show that these markers can be used to define distinct subsets in the circulation and lymph nodes during the acute phase and in "steady state" in humans. In contrast to the T cells in the circulation, T cells derived from lymph n ...[more]

PMID: 30883723

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Project description:BackgroundTuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is an inflammatory complication in HIV-TB co-infected patients receiving antiretroviral therapy (ART). The exact contribution of T cells, natural killer (NK) cells, and monocytes to TB-IRIS development remains unclear. Here, we studied the expression of exhaustion markers on lymphocytes at different intervals during ART.MethodsWe compared 13 HIV-TB patients who developed TB-IRIS with 13 patients who did not (HIV+TB+), 13 HIV-patients without TB (HIV+TB-) and 9 HIV/TB-negative controls (HIV-TB-). Patients did not differ in age, gender, or CD4-count prior to ART. Frozen peripheral blood mononuclear cells, collected before ART and during 3 months and 9 months of ART, were analysed using flow cytometry. We examined expression of KLRG1, PD-1 and IL-27R on CD4+ and CD8hi T cells, as well as CD3-negative CD8lo lymphocytes as an approximate subset of NK cells. In addition, expression of TLR2, TLR4, IL1RL1, and TRAILR on CD14+ monocytes were investigated.ResultsPrior to ART, TB-IRIS patients had higher percentages of CD8hi T cells that are KLRG1+PD-1+ compared to each control group (p≤0.034). Though PD-1 expression decreased during ART in all groups (p≤0.026), the percentage KLRG1+PD-1+CD8hi T cells remained higher in TB-IRIS patients after 3 months of ART (p≤0.013). Though these patterns were less pronounced in CD3-CD8lo lymphocytes, the percentage of KLRG1+ cells was higher in TB-IRIS patients prior to ART (p≤0.043). In contrast, no clear differences could be observed for CD4+ T cells or monocytes.ConclusionTB-IRIS is preceded by a high level of exhausted (KLRG1+PD-1+) CD8hi T cells, which persists during 3 months of ART. This trait is potentially mirrored in a subpopulation of NK cells, but not CD4+ T cells. Since a dysfunctional CD8+ lymphocyte compartment could predispose patients to TB-IRIS, the functional role of these cells prior to TB-IRIS development should be further explored.

Dataset Information

Expression of IL-7R? and KLRG1 defines functionally distinct CD8+ T-cell populations in humans.

Publications

Expression of IL-7Rα and KLRG1 defines functionally distinct CD8<sup>+</sup> T-cell populations in humans.

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