Small intestinal CD8+TCRγδ+NKG2A+ intraepithelial lymphocytes have attributes of regulatory cells in patients with celiac disease

Bhagat, Govind; Naiyer, Afzal J.; Shah, Jainil P.; Harper, Jason; Jabrì, Bana; Wang, Yichen; Green, Peter H.R.; Manavalan, John S.

doi:10.1172/jci30989

Cited by 173 publications

(162 citation statements)

References 66 publications

Supporting

Mentioning

146

Contrasting

Unclassified

Order By: Relevance

“…Moreover, our earlier work indicated that a CD2 + CD8 + subpopulation is more mature than CD2 + CD8 2 (12). Such a conclusion agrees with other studies in humans where CD8 + gd T cells were shown to have attributes of regulatory cells (37). Also, some studies indicate that CD2 + CD8 2 gd T cells can be precursors of CD2 + CD8 + gd T cells (10,38).…”

Section: Discussionsupporting

confidence: 90%

Porcine γδ T Lymphocytes Can Be Categorized into Two Functionally and Developmentally Distinct Subsets according to Expression of CD2 and Level of TCR

Štěpánová

Šinkora

2013

The Journal of Immunology

View full text Add to dashboard Cite

Porcine γδ T cells have two levels of TCRγδ expression. Whereas TCRγδmed cells are mostly CD2+CD8− and CD2+CD8+, TCRγδhi cells are highly enriched for CD2−CD8−. This distribution is independent of bacterial colonization and it is already established in the thymus prior to export of γδ cells to the periphery. Sorting and cultivation experiments revealed that CD2−CD8− γδ cells are unable to acquire CD2 and CD8, whereas CD2+ subsets can gain or loose CD8. There is also differential susceptibility for proliferation between CD2+ and CD2− γδ cells. Although CD2−CD8− almost do not proliferate, proliferation of CD2+CD8− and CD2+CD8+ is substantial. Population of CD2− γδ cells is also absent in CD1+ immature thymocytes. Additionally, subpopulations of CD2+ and CD2− γδ cells in the thymus differ in expression of auxiliary surface molecules such as CD25, CD45RA/RC, and MHC class II. Moreover, TCRγδhi cells can generate TCRγδmed cells but never the opposite. The only exception is the thymus, where a few TCRγδmed cells can be induced to TCRγδhi but only under IL-2 influence. The repertoire of TCRδ is polyclonal in all subsets, indicating that there is the same extent of diversification and equal capability of immune responses. Results collectively indicate that CD2 expression determines two lineages of γδ cells that differ in many aspects. Because CD2− γδ cells are missing in the blood of humans and mice but are obvious in other members of γδ-high species such as ruminants and birds, our findings support the idea that circulating CD2− γδ T cells are a specific lineage.

show abstract

Section: Discussionsupporting

confidence: 90%

Porcine γδ T Lymphocytes Can Be Categorized into Two Functionally and Developmentally Distinct Subsets according to Expression of CD2 and Level of TCR

Štěpánová

Šinkora

2013

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…In human CD, both cytotoxic and anti-inflammatory functions have been attributed to subsets of γδ IELs (35,36). In mice, γδ IELs appear to be constitutively activated with high cytotoxic potential at baseline (37).…”

Section: Discussionmentioning

confidence: 99%

Dietary gluten triggers concomitant activation of CD4 ⁺ and CD8 ⁺ αβ T cells and γδ T cells in celiac disease

Han

Newell

Glanville

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

176

146

View full text Add to dashboard Cite

Celiac disease is an intestinal autoimmune disease driven by dietary gluten and gluten-specific CD4 + T-cell responses. In celiac patients on a gluten-free diet, exposure to gluten induces the appearance of gluten-specific CD4 + T cells with gut-homing potential in the peripheral blood. Here we show that gluten exposure also induces the appearance of activated, gut-homing CD8 + αβ and γδ T cells in the peripheral blood. Single-cell T-cell receptor sequence analysis indicates that both of these cell populations have highly focused Tcell receptor repertoires, indicating that their induction is antigendriven. These results reveal a previously unappreciated role of antigen in the induction of CD8 + αβ and γδ T cells in celiac disease and demonstrate a coordinated response by all three of the major types of T cells. More broadly, these responses may parallel adaptive immune responses to viral pathogens and other systemic autoimmune diseases.autoimmunity | mucosal immunity

show abstract

“…Once activated, Vd1 + T cells can drive DC maturation [215] but also kill DCs [216]. In addition, Vd1 + T cells can display properties of regulatory T cells and suppress immune responses through contact or cytokine dependent interactions [217][218][219][220], including the suppression of DC maturation in breast cancer [221,222]. Thus, it appears that the Vd1 + , Vd2 + and Vd3 + subsets of cd T cells as well as iNKT cells all play roles in the induction, polarization and/or regulation of adaptive immune responses in humans.…”

Section: Innate Regulation Of Adaptive Immune Responses: Vd2 + Versusmentioning

confidence: 99%

Human Vγ9/Vδ2 T cells: Innate adaptors of the immune system

Tyler

Doherty

Moser

et al. 2015

Cellular Immunology

View full text Add to dashboard Cite

a b s t r a c tUnconventional T cells are gaining center stage as important effector and regulatory cells that orchestrate innate and adaptive immune responses. Human Vc9/Vd2 T cells are amongst the best understood unconventional T cells, as they are easily accessible in peripheral blood, can readily be expanded and manipulated in vitro, respond to microbial infections in vivo and can be exploited for novel tumor immunotherapies. We here review findings that suggest that Vc9/Vd2 T cells, and possibly other unconventional human T cells, play an important role in bridging innate and adaptive immunity by promoting the activation and differentiation of various types of antigen-presenting cells (APCs) and even turning into APCs themselves, and thereby pave the way for antigen-specific effector responses and long-term immunological memory. Although the direct physiological relevance for most of these mechanisms still needs to be demonstrated in vivo, these findings may have implications for novel therapies, diagnostic tests and vaccines.Ó 2015 Published by Elsevier Inc. Introduction cd T cells represent a third lineage of lymphocytes expressingre-arranged antigen receptors that co-evolved with 'classical' B cells and ab T cells over 400 million years, arguing for a crucial and non-redundant contribution of each lymphocyte to effective immune responses, and hence the evolutionary survival of all jawed vertebrate species [1]. 30 years have passed since the accidental and unexpected cloning of the cd T cell receptor (TCR) and the subsequent realization that ab T cells and cd T cells are fundamentally different with respect to the types of antigens they recognize and the distinct effector functions triggered upon such recognition. However, the manifold contributions of cd T cells to homeostasis, inflammation, infection and tumor surveillance have historically been neglected and are only beginning to be integrated into comprehensive models of the immune system [1][2][3][4][5][6][7].1. Innate-like pattern recognition by human Vc9/Vd2 T cells Like other 'unconventional' T cells carrying an ab TCR such as mucosal-associated invariant T (MAIT) cells and natural killer T (NKT) cells, cd T cells are characterized by a markedly restrictedTCR usage that allows them to recognize self and non-self molecules in the absence of classical antigen presentation via MHC I or MHC II. Vc9/Vd2 + cd T cells represent the major cd T cell subset in human peripheral blood where they typically comprise 1-5% in healthy adults [8]. In many microbial infections, Vc9/Vd2 T cells increase locally and/or systemically [9,10] and can reach in excess of 50% of all peripheral T cells within a matter of days [11], revealing a fundamental role of this unconventional T cell population in acute disease and suggesting their exploitation for diagnostic and therapeutic purposes [12][13][14]. Vc9/Vd2 T cells uniformly respond to a class of low molecular weight molecules often referred to as 'phosphoantigens' that represent metabolites of the isoprenoid biosynthesis...

show abstract

Small intestinal CD8+TCRγδ+NKG2A+ intraepithelial lymphocytes have attributes of regulatory cells in patients with celiac disease

Cited by 173 publications

References 66 publications

Porcine γδ T Lymphocytes Can Be Categorized into Two Functionally and Developmentally Distinct Subsets according to Expression of CD2 and Level of TCR

Porcine γδ T Lymphocytes Can Be Categorized into Two Functionally and Developmentally Distinct Subsets according to Expression of CD2 and Level of TCR

Dietary gluten triggers concomitant activation of CD4 ⁺ and CD8 ⁺ αβ T cells and γδ T cells in celiac disease

Human Vγ9/Vδ2 T cells: Innate adaptors of the immune system

Contact Info

Product

Resources

About

Small intestinal CD8+TCRγδ+NKG2A+ intraepithelial lymphocytes have attributes of regulatory cells in patients with celiac disease

Cited by 173 publications

References 66 publications

Porcine γδ T Lymphocytes Can Be Categorized into Two Functionally and Developmentally Distinct Subsets according to Expression of CD2 and Level of TCR

Porcine γδ T Lymphocytes Can Be Categorized into Two Functionally and Developmentally Distinct Subsets according to Expression of CD2 and Level of TCR

Dietary gluten triggers concomitant activation of CD4 + and CD8 + αβ T cells and γδ T cells in celiac disease

Human Vγ9/Vδ2 T cells: Innate adaptors of the immune system

Contact Info

Product

Resources

About

Dietary gluten triggers concomitant activation of CD4 ⁺ and CD8 ⁺ αβ T cells and γδ T cells in celiac disease