Role of &amp;#946;7 Integrins in Intestinal Lymphocyte Homing and Retention

Gorfu, Gezahegn; Rivera–Nieves, Jesús; Ley, Klaus

doi:10.2174/156652409789105525

Cited by 270 publications

(222 citation statements)

References 210 publications

(284 reference statements)

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“…3A). β7 integrin is a cell adhesion molecule that is important in mediating efficient homing and retention of lymphocytes into the gut (28). Higher expression of β7 integrin on the surface of D7 TEC s agrees with our earlier observation that D7 TEC s traffic more efficiently to the gut than D7 HC s, suggesting that these two phenotypically distinct T-cell subsets might play distinct immunological roles.…”

Section: D7 Cd8 + T Cells Selected On Hcs Are More Activated Than Thosesupporting

confidence: 89%

Positive selecting cell type determines the phenotype of MHC class Ib-restricted CD8 ⁺ T cells

Cho

Bediako

et al. 2011

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

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Several studies have demonstrated an apparent link between positive selection on hematopoietic cells (HCs) and an “innate” T-cell phenotype. Whereas conventional CD8 + T cells are primarily selected on thymic epithelial cells (TECs) and certain innate T cells are exclusively selected on HCs, MHC class Ib-restricted CD8 + T cells appear to be selected on both TECs and HCs. However, whether TEC- and HC-selected T cells represent distinct lineages or whether the same T-cell precursors have the capacity to be selected on either cell type is unknown. Using an M3-restricted T-cell receptor transgenic mouse model, we demonstrate that not only are MHC class Ib-restricted CD8 + T cells capable of being selected on either cell type but that selecting cell type directly affects the phenotype of the resulting CD8 + T cells. M3-restricted CD8 + T cells selected on HCs acquire a more activated phenotype and possess more potent effector functions than those selected on TECs. Additionally, these two developmental pathways are active in the generation of the natural pool of M3-restricted CD8 + T cells. Our results suggest that these two distinct populations may allow MHC class Ib-restricted CD8 + T cells to occupy different immunological niches playing unique roles in immune responses to infection.

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Section: D7 Cd8 + T Cells Selected On Hcs Are More Activated Than Thosesupporting

confidence: 89%

Positive selecting cell type determines the phenotype of MHC class Ib-restricted CD8 ⁺ T cells

Cho

Bediako

et al. 2011

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

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“…Purified antibodies (lacking carrier proteins) were labeled 100 μg at a time according to instructions provided by DVS Sciences with heavy metal-preloaded maleimide-coupled MAXPAR chelating polymers via Pre-Load Method version 2.1 (16).…”

Section: Methodsmentioning

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.

183

146

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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

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“…a E (CD103)b 7 is widely expressed by intraepithelial lymphocytes (IEL) in the skin and gut mucosa (24,25) and is thought to mediate the retention of T cells in relevant peripheral tissues by binding to E-cadherin expressed on the surface of epithelial cells (26). a E (CD103)b 7 has also been shown to enhance the cytolytic activity of T cells against E-cadherinexpressing tumor cells in vitro (27)(28)(29).…”

Section: Introductionmentioning

confidence: 99%

PD-1 and CD103 Are Widely Coexpressed on Prognostically Favorable Intraepithelial CD8 T Cells in Human Ovarian Cancer

Webb

Milne

Nelson

2015

Cancer Immunology Research

170

141

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a E (CD103)b 7 is a TGFb-regulated integrin that mediates retention of lymphocytes in peripheral tissues by binding to E-cadherin expressed on epithelial cells. We recently reported that a E (CD103)b 7 specifically demarcates intraepithelial CD8 þ tumor-infiltrating lymphocytes (CD8 TIL) in ovarian cancer and that CD103 þ TIL have a surface profile consistent with an active effector phenotype (HLA-DR þ , Ki67 þ , and CD127 lo ). These findings led us to hypothesize that, over time, CD103-mediated retention of CD8 TIL within the tumor epithelium might result in chronic stimulation by tumor antigen, which in turn might lead to an exhausted phenotype. To investigate this possibility, we evaluated PD-1 expression in a large cohort of ovarian tumors (N ¼ 489) with known CD103 þ TIL content. PD-1 þ cells were present in 38.5% of high-grade serous carcinomas (HGSC), but were less prevalent in other histologic subtypes. PD-1 þ TIL were strongly associated with increased disease-specific survival in HGSC (HR, 0.4864; P ¼ 0.0007). Multicolor immunohistochemistry and flow cytometry revealed a high degree of PD-1 and CD103 coexpression, specifically within the CD8 TIL compartment. PD-1 þ CD103 þ CD8 TIL were quiescent when assessed directly ex vivo yet were capable of robust cytokine production after pharmacologic stimulation. Moreover, they showed negligible expression of additional exhaustion-associated markers, including TIM-3, CTLA-4, and LAG-3. Thus, as hypothesized, CD103 þ CD8 TIL express PD-1 and appear quiescent in the tumor microenvironment. However, these cells retain functional competence and demonstrate strong prognostic significance. We speculate that, after standard treatment, PD-1 þ CD103 þ CD8 TIL might regain functional antitumor activity, an effect that potentially could be augmented by immune modulation. Cancer Immunol Res; 3(8); 926-35. Ó2015 AACR.

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Role of β7 Integrins in Intestinal Lymphocyte Homing and Retention

Cited by 270 publications

References 210 publications

Positive selecting cell type determines the phenotype of MHC class Ib-restricted CD8 ⁺ T cells

Positive selecting cell type determines the phenotype of MHC class Ib-restricted CD8 ⁺ T cells

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

PD-1 and CD103 Are Widely Coexpressed on Prognostically Favorable Intraepithelial CD8 T Cells in Human Ovarian Cancer

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Role of &#946;7 Integrins in Intestinal Lymphocyte Homing and Retention

Cited by 270 publications

References 210 publications

Positive selecting cell type determines the phenotype of MHC class Ib-restricted CD8 + T cells

Positive selecting cell type determines the phenotype of MHC class Ib-restricted CD8 + T cells

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

PD-1 and CD103 Are Widely Coexpressed on Prognostically Favorable Intraepithelial CD8 T Cells in Human Ovarian Cancer

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Resources

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Role of β7 Integrins in Intestinal Lymphocyte Homing and Retention

Positive selecting cell type determines the phenotype of MHC class Ib-restricted CD8 ⁺ T cells

Positive selecting cell type determines the phenotype of MHC class Ib-restricted CD8 ⁺ T cells

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