Peripheral CD4+CD8+ T cells are differentiated effector memory cells with antiviral functions

Nascimbeni, Michelina; Shin, Eui‐Cheol; Chiriboga, Luis; Kleiner, David E.; Rehermann, Barbara

doi:10.1182/blood-2003-12-4395

Cited by 221 publications

(268 citation statements)

References 40 publications

(42 reference statements)

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“…Very low percentages of double positive CD41CD81 are normally found in humans (26). We note that the CD4-AmCyan results in a reasonable separation of CD41 T lymphocytes in normal blood, but may present a problem if CD4 is significantly down-regulated in specimens from samples of patients with Acquired Immune Deficiency Syndrome (AIDS).…”

Section: Panel Strategy and Developmentmentioning

confidence: 84%

Evaluation of a 12‐color flow cytometry panel to study lymphocyte, monocyte, and dendritic cell subsets in humans

et al. 2010

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Monitoring changes in human immune cell populations such as lymphocytes, monocytes, and dendritic cells (DCs) during infectious diseases like human immunodeficiency virus (HIV) is crucial. However, difficulties to identify rare or heterogeneous cell populations can be limiting. For example, to accurately measure DC subsets, eight flow cytometry parameters are ideal. The aim of this work was to analyze the phenotype of human lymphocyte, monocyte, and DC subsets using a single 12-color flow cytometry panel. After erythrocyte lysis, blood from healthy human volunteers was washed and labeled with a cocktail of 12 antibodies. Samples were analyzed on a Becton-Dickinson FACSAria TM equipped with three lasers. Data were compared with lineage-specific panels using 5-8 Ab combinations per lineage. Acquired data were analyzed using FlowJo software. Our 12-color panel allows for the identification of the following major subsets of circulating cells in a single tube: CD41 and CD81 T lymphocytes, B lymphocytes, NK cells, NKT cells, monocyte subsets (CD14 and/or CD16), and five nonoverlapping HLA-DR1Lin2 subsets: CD341 hematopoietic stem cells, CD1231 plasmacytoid DC, and three subsets of CD11c1 myeloid DC expressing either CD16, CD1c (BDCA-1), or CD141 (BDCA-3). We have developed a single flow cytometry panel that allows for simultaneous detection of the lymphocyte and monocyte cell populations and all known DC subsets. Studying these major players of the immune system in one single panel may give us a broader view of the immune response during HIV infection and the ability to better define the role of individual cell types in Acquired Immune Deficiency Syndrome (AIDS) pathogenesis. ' 2010 International Society for Advancement of Cytometry

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Section: Panel Strategy and Developmentmentioning

confidence: 84%

Evaluation of a 12‐color flow cytometry panel to study lymphocyte, monocyte, and dendritic cell subsets in humans

et al. 2010

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“…[42][43][44] Of interest, it has been shown that DP T cells play an important regulatory role in inflammatory bowel disease 33 and may contribute to the adaptative immune response during viral infections. 45 However, little is known regarding their function in cancer, except for one study describing the capacity of DP T cells infiltrating a cutaneous T-cell lymphoma to exert a tumor-specific HLA Class I restricted lysis. 46 In agreement with what was observed for intestinal DP T cells, breast tumor associated DP T cells have an overall higher capacity to produce cytokines than SP T cells.…”

Section: Discussionmentioning

confidence: 99%

Increased frequency of nonconventional double positive CD4CD8 αβ T cells in human breast pleural effusions

Desfrançois

Derré

Corvaisier

et al. 2009

Intl Journal of Cancer

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Breast cancer remains a leading cause of cancer-related death within the female population. Immunotherapy is expected to provide additional therapeutic benefits but has met so far limited success. This may be due in part to the poor understanding of immune responses to breast cancer. Although CD4 1 and CD8 1 T lymphocytes infiltrate these tumors, the phenotype and functions of these cells remain ill defined. This study was designed to investigate further about these questions, taking advantage of multiparameter flow cytometry on lymphocytes derived from peripheral blood, solid tumors, metastatic lymph nodes and pleural effusions samples of patients with breast cancer. Results showed that, in addition to conventional CD4 1 and CD8 1 ab T cells, individual tumors and most pleural effusions contained significant fractions of unconventional double positive (DP) CD4 1 CD8 1 ab T cells. These DP T cells displayed the phenotype and cytotoxic potential of effector/memory activated CD8 1 T cells but differed essentially from these cells by a high production of IL-5 and IL-13. The increased frequency of DP T cells in advanced breast cancer and their high lytic potential and original cytokine profile suggest that this T-cell subset may play a specific role in the regulation of immune responses to human breast cancer. ' 2009 UICC

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“…Of interest, numerous studies reported the presence of DP T cells with, in most cases, an increased frequency in the blood and/or in the target organ of several pathological conditions (for review see [9]), such as autoimmune diseases [10][11][12], inflammation disorders [13,14], allergies [15,16], infectious diseases [17][18][19], and cancer, postulating their involvement in pathologic events [20][21][22][23]. In these contexts, diverse functions of DP T cells were observed from cytotoxic activity [22,24] to regulatory properties [25], as well as helper potential [10].…”

Section: Introductionmentioning

confidence: 99%

IL‐9 promotes the survival and function of human melanoma‐infiltrating CD4⁺CD8⁺ double‐positive T cells

et al. 2016

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We previously demonstrated an accumulation of tumor-reactive CD4 + CD8 + double positive (DP) T cells within melanoma-infiltrating lymphocytes, supporting their role in the regulation of anti-tumor immune responses. Similarly to their CD8 + counterparts, intratumor DP T cells are MHC class-I restricted but differed by a limited lytic activity against autologous melanoma cells. Based on these observations and to further characterize DP T cells, both populations were compared at the transcriptional level. Our results revealed the overexpression of the IL-9 receptor (IL-9R) by DP T cells and prompted us to investigate the impact of IL-9 on their biology. We show that IL-9 favors DP T-cell survival by protecting them from apoptosis and by promoting their proliferation. In addition, IL-9 enhances their ability to produce cytokines and increased their levels of granzyme B/perforin as well as degranulation capacity, leading to a strengthened cytotoxic activity against melanoma cells. Taken together, the IL-9R high DP T-cell population could be a new preferential target for IL-9, which could take part in their retention within the melanoma infiltrate while also favoring their anti-tumor activity. More generally, our results extend the pleiotropic effects of IL-9 to IL-9R-expressing intra-tumor T cells, which could further potentiate anti-tumor immune responses.Keywords: CD4 + CD8 + double-positive T lymphocyte r IL-9R r IL-9 r Melanoma r TIL Additional supporting information may be found in the online version of this article at the publisher's web-site Correspondence: Dr. Nadine Gervois e-mail: nadine.gervois@inserm.fr IntroductionPeripheral CD4 + CD8 + double-positive (DP) T cells were first identified 25 years ago as a mature T-cell subpopulation accounting for about 1-2% of total T cells within healthy donor PBMCs Eur. J. Immunol. 2016Immunol. . 46: 1770Immunol. -1782 Tumor immunology 1771 with age-dependent increase [2]. Since then, DP T cells have been described as a highly heterogeneous population with at least three subsets based on the expression levels of the CD4 and the CD8 coreceptors (CD4 high CD8 low , CD4 low CD8 high , CD4 high CD8 high ) and on the nature of the CD8 dimer (αα or αβ) [3]. Regarding DP T cells lineage origin, two main hypotheses are still in debate. Some studies argued they step from a premature release of DP T cells from the thymus into the periphery, where their maturation into functionally competent single-positive (SP) cells continues [4,5].Others studies hypothesized that they could derive from peripheral single positive T cells. As such, IL-4 represents an important mediator of CD8αα induction on human SP CD4 T cells [6]. On the other hand, when activated in vitro via TCR cross-linking, SP CD8αβ T cells may become capable of expressing low levels of CD4 [7,8].Of interest, numerous studies reported the presence of DP T cells with, in most cases, an increased frequency in the blood and/or in the target organ of several pathological conditions (for review see [9]), such as autoimmune ...

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Peripheral CD4+CD8+ T cells are differentiated effector memory cells with antiviral functions

Cited by 221 publications

References 40 publications

Evaluation of a 12‐color flow cytometry panel to study lymphocyte, monocyte, and dendritic cell subsets in humans

Evaluation of a 12‐color flow cytometry panel to study lymphocyte, monocyte, and dendritic cell subsets in humans

Increased frequency of nonconventional double positive CD4CD8 αβ T cells in human breast pleural effusions

IL‐9 promotes the survival and function of human melanoma‐infiltrating CD4⁺CD8⁺ double‐positive T cells

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Peripheral CD4+CD8+ T cells are differentiated effector memory cells with antiviral functions

Cited by 221 publications

References 40 publications

Evaluation of a 12‐color flow cytometry panel to study lymphocyte, monocyte, and dendritic cell subsets in humans

Evaluation of a 12‐color flow cytometry panel to study lymphocyte, monocyte, and dendritic cell subsets in humans

Increased frequency of nonconventional double positive CD4CD8 αβ T cells in human breast pleural effusions

IL‐9 promotes the survival and function of human melanoma‐infiltrating CD4+CD8+ double‐positive T cells

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IL‐9 promotes the survival and function of human melanoma‐infiltrating CD4⁺CD8⁺ double‐positive T cells