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PLZF-expressing CD4 T cells show the characteristics of terminally differentiated effector memory CD4 T cells in humans.

ABSTRACT: We show the presence of lymphoid tissue-resident PLZF+ CD45RA+ RO+ CD4 T cells in humans. They express HLA-DR, granzyme B, and perforin and are low on CCR7 like terminally differentiated effector memory (Temra) cells and are likely generated from effector T cells (Te) or from central (Tcm) or effector (Tem) memory T (Tcm) cells during immune responses. Tn, Naïve T cells.

SUBMITTER: Kim YH

PROVIDER: S-EPMC6748641 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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PLZF-expressing CD4 T cells show the characteristics of terminally differentiated effector memory CD4 T cells in humans.

Kim Yeung-Hyen YH Zhu Lingqiao L Pyaram Kalyani K Lopez Cesar C Ohye Richard G RG Garcia J Victor JV Green Glenn E GE Chang Cheong-Hee CH

European journal of immunology 20180430 7

We show the presence of lymphoid tissue-resident PLZF+ CD45RA+ RO+ CD4 T cells in humans. They express HLA-DR, granzyme B, and perforin and are low on CCR7 like terminally differentiated effector memory (Temra) cells and are likely generated from effector T cells (Te) or from central (Tcm) or effector (Tem) memory T (Tcm) cells during immune responses. Tn, Naïve T cells. ...[more]

PMID: 29572809

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Project description:The cardiovascular and immune systems undergo profound and intertwined alterations with aging. Recent studies have reported that an accumulation of memory and terminally differentiated T cells in elderly subjects can fuel myocardial aging and boost the progression of heart diseases. Nevertheless, it remains unclear whether the immunological senescence profile is sufficient to cause age-related cardiac deterioration or merely acts as an amplifier of previous tissue-intrinsic damage. Herein, we sought to decompose the causality in this cardio-immune crosstalk by studying young mice harboring a senescent-like expanded CD4+ T cell compartment. Thus, immunodeficient NSG-DR1 mice expressing HLA-DRB1*01:01 were transplanted with human CD4+ T cells purified from matching donors that rapidly engrafted and expanded in the recipients without causing xenograft reactions. In the donor subjects, the CD4+ T cell compartment was primarily composed of naïve cells defined as CCR7+CD45RO-. However, when transplanted into young lymphocyte-deficient mice, CD4+ T cells underwent homeostatic expansion, upregulated expression of PD-1 receptor and strongly shifted towards effector/memory (CCR7- CD45RO+) and terminally-differentiated phenotypes (CCR7-CD45RO-), as typically seen in elderly. Differentiated CD4+ T cells also infiltrated the myocardium of recipient mice at comparable levels to what is observed during physiological aging. In addition, young mice harboring an expanded CD4+ T cell compartment showed increased numbers of infiltrating monocytes, macrophages and dendritic cells in the heart. Bulk mRNA sequencing analyses further confirmed that expanding T-cells promote myocardial inflammaging, marked by a distinct age-related transcriptomic signature. Altogether, these data indicate that exaggerated CD4+ T-cell expansion and differentiation, a hallmark of the aging immune system, is sufficient to promote myocardial alterations compatible with inflammaging in juvenile healthy mice.

Project description:BackgroundIdentifying biomarkers to predict kidney transplant failure and to define new therapeutic targets requires more comprehensive understanding of the immune response to chronic allogeneic stimulation.MethodsWe investigated the frequency and function of CD8+ T cell subsets-including effector memory (EM) and terminally differentiated EM (TEMRA) CD8+ T cells-in blood samples from 284 kidney transplant recipients recruited 1 year post-transplant and followed for a median of 8.3 years. We also analyzed CD8+ T cell reactivity to donor-specific PBMCs in 24 patients who had received living-donor kidney transplants.ResultsIncreased frequency of circulating TEMRA CD8+ T cells at 1 year post-transplant associated with increased risk of graft failure during follow-up. This association remained after adjustment for a previously reported composite of eight clinical variables, the Kidney Transplant Failure Score. In contrast, increased frequency of EM CD8+ T cells associated with reduced risk of graft failure. A distinct TEMRA CD8+ T cell subpopulation was identified that was characterized by expression of FcγRIIIA (CD16) and by high levels of proinflammatory cytokine secretion and cytotoxic activity. Although donor-specific stimulation induced a similar rapid, early response in EM and TEMRA CD8+ T cells, CD16 engagement resulted in selective activation of TEMRA CD8+ T cells, which mediated antibody-dependent cytotoxicity.ConclusionsAt 1 year post-transplant, the composition of memory CD8+ T cell subsets in blood improved prediction of 8-year kidney transplant failure compared with a clinical-variables score alone. A subpopulation of TEMRA CD8+ T cells displays a novel dual mechanism of activation mediated by engagement of the T-cell receptor or of CD16. These findings suggest that TEMRA CD8+ T cells play a pivotal role in humoral and cellular rejection and reveal the potential value of memory CD8+ T cell monitoring for predicting risk of kidney transplant failure.

Dataset Information

PLZF-expressing CD4 T cells show the characteristics of terminally differentiated effector memory CD4 T cells in humans.

Publications

PLZF-expressing CD4 T cells show the characteristics of terminally differentiated effector memory CD4 T cells in humans.

Similar Datasets

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