CD8αβ+ γδ T Cells: A Novel T Cell Subset with a Potential Role in Inflammatory Bowel Disease

Kadivar, Mohammad; Petersson, Julia; Svensson, Lena; Marsal, Jan

doi:10.4049/jimmunol.1601146

Cited by 70 publications

(56 citation statements)

References 53 publications

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“…Another study later identified a population of high cytotoxic and immune-regulatory intestinal CD8 + γδ T cells carrying the heterodimer CD8αβ. This latter immunoregulatory subset plays a key role in the homeostasis of gut-associated lymphoid tissue and in the pathogenesis of inflammatory bowel disease (IBD) (26). Our results showed that, while the entire population of CD8 + γδ IELs express significantly higher levels of α rather than β chain, the subset of NKp46 + /CD8 + γδ IELs coexpresses similar levels of α and β chains in their CD8 receptor ( Figure 1F).…”

Section: Resultsmentioning

confidence: 84%

NKp46-expressing human gut-resident intraepithelial Vδ1 T cell subpopulation exhibits high antitumor activity against colorectal cancer

Mikulak¹,

Oriolo²,

Bruni³

et al. 2019

JCI Insight

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103

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Section: Resultsmentioning

confidence: 84%

NKp46-expressing human gut-resident intraepithelial Vδ1 T cell subpopulation exhibits high antitumor activity against colorectal cancer

Mikulak¹,

Oriolo²,

Bruni³

et al. 2019

JCI Insight

100

103

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“…Previous studies have reported that 20%-30% of peripheral blood γδ Tc are CD8+low, [188,194] expressing CD8α and CD8β polypeptides in all possible combinations, with the largest proportion of cells (44% ± 17%) exhibiting CD8ββ homodimers and smaller fractions expressing CD8αα homodimers (14% ± 12%) or CD8αβ heterodimers (14% ± 12%, and that the mean fluorescence intensity of CD8 expression is much lower in CD8αα and CD8ββ γδ Tc [181]. One study showed that CD8αβ+ γδ Tc were enriched within the gut mucosa comparatively to the PB; they expressed cytotoxic cell-associated markers, such as the CD56 adhesion molecule; and cytotoxic granule proteins, such as granzyme B and perforin; they produced mainly IFN-γ and TNF-α, and, in the PB, they were mostly Vδ1 [195]. This could explain why we observed that in nearly half of the normal PB samples analyzed, part of the Vδ1, but not of Vδ2 Tc, had high and homogeneous CD8 expression, at levels that approximated to those observed in CD8+high αβ Tc.…”

Section: Cd8 Accessory Moleculementioning

confidence: 99%

Human Peripheral Blood Gamma Delta T Cells: Report on a Series of Healthy Caucasian Portuguese Adults and Comprehensive Review of the Literature

Fonseca

Pereira

Lau

et al. 2020

Cells

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Gamma delta T cells (Tc) are divided according to the type of Vδ and Vγ chains they express, with two major γδ Tc subsets being recognized in humans: Vδ2Vγ9 and Vδ1. Despite many studies in pathological conditions, only a few have quantified the γδ Tc subsets in healthy adults, and a comprehensive review of the factors influencing its representation in the blood is missing. Here we quantified the total γδ Tc and the Vδ2/Vγ9 and Vδ1 Tc subsets in the blood from 30 healthy, Caucasian, Portuguese adults, we characterized their immunophenotype by 8-color flow cytometry, focusing in a few relevant Tc markers (CD3/TCR-γδ, CD5, CD8), and costimulatory (CD28), cytotoxic (CD16) and adhesion (CD56) molecules, and we examined the impacts of age and gender. Additionally, we reviewed the literature on the influences of race/ethnicity, age, gender, special periods of life, past infections, diet, medications and concomitant diseases on γδ Tc and their subsets. Given the multitude of factors influencing the γδ Tc repertoire and immunophenotype and the high variation observed, caution should be taken in interpreting "abnormal" γδ Tc values and repertoire deviations, and the clinical significance of small populations of "phenotypically abnormal" γδ Tc in the blood.Cells 2020, 9, 729 2 of 40 associates with Vγ9 in most cases, defining a Vγ9Vδ2 Tc population that is unique to humans and other primates, whereas Vδ1 Tc use diverse Vγ regions [4][5][6].Gamma delta Tc is involved in the immune response to viruses, intracellular bacteria, and parasitic protozoa [7][8][9][10][11][12][13][14]; is involved in immune surveillance against hematological neoplasms and solid tumors [15][16][17] and the pathogenesis of autoimmune diseases [18,19]; and abnormal percentages and/or absolute numbers of γδ Tc involving different γδ Tc subsets have been reported in the PB and in different organs from patients with various pathological conditions. Vδ2 Tc respond mainly to intracellular bacteria and solid tumors, while Vδ1 Tc, resident mainly in tissues, is used mostly in the defense against viruses and malignancies, although this dichotomy is not absolute. In addition, γδ T-cells are being explored in cell-based immunotherapy [20][21][22].In parallel to the low frequency of γδ Tc, lymphoproliferative disorders (LPD) of γδ Tc are rare disease conditions. These comprise γδ Tc large granular lymphocyte (LGL) proliferations, including γδ Tc LGL leukemia, defined as clonal expansions of cytotoxic γδ Tc, which have an indolent clinical course and often coexist with cytopenias and other pathologies [23,24], and hepatosplenic and other γδ Tc lymphomas, which usually have an aggressive clinical course, poor response to chemotherapy and short survival [25][26][27][28].Gamma delta Tc expressing Vγ9Vδ2 are known to identify microbe-derived (e.g., (E)-4-hydroxy-3methyl-but-2-enyl pyrophosphate, HMB-PP) and host-derived (e.g., isopentenyl pyrophosphate, IPP) phosphorylated metabolites ("phosphoantigens") originating from the isoprenoid metabolic mevalonate and non-me...

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“…Reports have shown that CD8 + γδ T cells selectively localize to intestinal epithelial tissue and are mostly Vδ1 + [23,24]. Furthermore, a potential role in intestinal inflammatory diseases has been recently described [15]. In line with previous report, we showed that CD8 + γδ T cells are more frequent in CMV+ grafts [25] and express Vγ9γδ T cells.…”

supporting

confidence: 91%

CD8+γδ T cells are more frequent in CMV seropositive bone marrow grafts and display phenotype of an adaptive immune response

Gaballa¹,

Arruda²,

Radestad³

et al.

immuneACCESS

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The role of gamma delta (γδ) T cells in human cytomegalovirus (HCMV) immune surveillance has been the focus of research interest for years. Recent reports have shown a substantial clonal proliferation of γδ T cells in response to HCMV, shedding light on the adaptive immune response of γδ T cells. Nevertheless, most efforts have focused on Vδ2 neg γδ T cell subset while less attention has been given to investigate other less common γδ T cell subsets. In this regard, a distinct subpopulation of γδ T cells that expresses the CD8 coreceptor (CD8 + γδ T cells) has not been thoroughly explored. Whether it is implicated in HCMV response and its ability to generate adaptive response has not been thoroughly investigated. In this study, we combined flow cytometry and immune sequencing of the TCR γ-chain (TRG) to analyze in-depth bone marrow (BM) graft γδ T cells from CMV seropositive (CMV+) and CMV seronegative (CMV-) donors. We showed that the frequency of CD8 + γδ T cells was significantly higher in CMV+ grafts compared to CMV-grafts (P < 0:001). Further characterization revealed that CD8 + γδ T cells from CMV+ grafts express Vγ9and preferentially differentiated from a naive to terminal effector memory phenotype (CD27 low/-CD45RO-). In line with these findings, TRG immune sequencing revealed clonal focusing and reduced usage of the Vγ9/JP gene segment in a CMV+ graft. Furthermore, CD8 + γδ T cells showed an enhanced response to TCR/CD3 and cytokine stimulation in contrast to CD8γδ T cells. We conclude that γδ T cells in BM grafts are reshaped by donor CMV serostatus and highlight the potential adaptive role of CD8 + γδ T cells in HCMV immune response.

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CD8αβ+ γδ T Cells: A Novel T Cell Subset with a Potential Role in Inflammatory Bowel Disease

Cited by 70 publications

References 53 publications

NKp46-expressing human gut-resident intraepithelial Vδ1 T cell subpopulation exhibits high antitumor activity against colorectal cancer

NKp46-expressing human gut-resident intraepithelial Vδ1 T cell subpopulation exhibits high antitumor activity against colorectal cancer

Human Peripheral Blood Gamma Delta T Cells: Report on a Series of Healthy Caucasian Portuguese Adults and Comprehensive Review of the Literature

CD8+γδ T cells are more frequent in CMV seropositive bone marrow grafts and display phenotype of an adaptive immune response

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