A monoclonal antibody (HML‐1) defining a novel membrane molecule present on human intestinal lymphocytes

Cerf‐Bensussan, Nadine; Jarry, Anne; Brousse, Nicole; Lisowska-Grospierre, B; Guy‐Grand, Delphine; Griscelli, C

doi:10.1002/eji.1830170910

Cited by 407 publications

(246 citation statements)

References 40 publications

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“…We also investigated expression of CD103 antigen, a marker specific for IEL. 22 The antigen was expressed on the leukemic cells from two T-PLL cases and one ATLL case. CD45RO, preferentially expressed on memory T cells, was detected on DP T cells from five of six cases tested.…”

Section: Resultsmentioning

confidence: 98%

“…IEL is a distinct T cell subset that preferentially expresses CD8␣␣ subunits and contains a CD4 + , CD8␣␣ + population. We investigated expression of CD103, characteristic of IEL, 22 in DP ATLL cells. The antigen was detected in only one of the DP ATLL cases, weakly, and none of the three ATLL cases showed primary involvement in the intestinal tract.…”

Section: Tablementioning

confidence: 99%

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Phenotypical heterogeneity of CD4+CD8+ double-positive chronic T lymphoid leukemia

et al. 1998

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Chronic T lymphoid leukemias are defined as leukemias of post-thymic T cells. The CD4 ؉ CD8 ؉ double-positive (DP) phenotype is seen in a few cases. Since DP generally occurs in thymic T cells, whether the DP T leukemia cells represent thymic or peripheral T cells has been a matter of controversy. To address this issue, we studied phenotypical features in eight cases of DP T cell leukemia. Thymic DP T cells and peripheral CD8 ؉ T cells have CD8 of ␣␤ subunit, while CD8␣␣ is induced in CD4 ؉ T cells on activation with IL-4. We found that two patients with DP T large granular lymphocyte leukemia (LGLL) showed dim expression of CD8␣␣, identical to the phenotype on IL-4-activated DP-T cells. The leukemic cells of these patients expressed IL-4 mRNA and produced high levels of IL-4. These findings suggest that they may be derived from peripheral CD4 ؉ T cells. Three patients with adult T cell leukemia/lymphoma (ATLL) showed CD8␣␣, suggestive of an activated peripheral T cell origin. One case expressed CD8␣␣ dim and IL-4 mRNA, while the other two cases expressed no IL-4 mRNA and showed CD8␣␣ bright phenotype, features not found in normal T cell populations. Three patients with T-prolymphocytic leukemia (T-PLL) expressed CD8␣␤. The DP phenotype is relatively common in T-PLL, and CD4 + CD8␣␤ + is characteristic of thymic T cells. The DP T-PLL cells did not express TdT,CD1 or recombination activating gene-1 (RAG-1), which is down-regulated at the late stage of thymic T cell development. On the basis of these findings, we propose a late thymic origin for DP T-PLL. The phenotype of DP T cells differed for each entity and appeared to correlate with minor normal DP T cell population.

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Section: Resultsmentioning

confidence: 98%

Section: Tablementioning

confidence: 99%

Phenotypical heterogeneity of CD4+CD8+ double-positive chronic T lymphoid leukemia

et al. 1998

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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

165

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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“…The integrin ␣ E ␤ 7 was initially described as a marker for intraepithelial T cells residing in the gut wall and other epithelial compartments such as skin or lung (36,37). Whereas the related integrin ␣ 4 ␤ 7 serves as a homing receptor for mucosa-seeking populations by recognizing mucosal addressin cell adhesion molecule-1 (MAdCAM-1) (38), the only ligand for ␣ E ␤ 7 clearly identified so far is E-cadherin, expressed on epithelial cells but not on endothelium (39).…”

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confidence: 99%

Expression of the integrin α_Eβ₇identifies unique subsets of CD25⁺as well as CD25⁻regulatory T cells

Lehmann

Huehn

Rosa

et al. 2002

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

431

388

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Regulatory CD25 ؉ CD4 ؉ T cells are considered as important players in T cell homeostasis and self-tolerance. Here we report that the integrin ␣E␤7, which recognizes epithelial cadherin, identifies the most potent subpopulation of regulatory CD25 ؉ T cells. Strikingly, CD25-negative ␣E ؉ CD4 ؉ T cells displayed regulatory activity. Both ␣E ؉ subsets, CD25 ؉ and CD25 ؊ , express CTLA-4, suppress T cell proliferation in vitro, and protect mice from colitis in the severe combined immunodeficient model (SCID) in vivo. Whereas ␣E ؉ CD25 ؉ T cells produce almost no cytokines, ␣E ؉ CD25 ؊ T cells represent a unique subset in which high IL-2, IFN-␥ and T helper 2-cytokine production is linked with suppressive function. Thus, the integrin ␣E␤7 can be regarded as a novel marker for subsets of highly potent, functionally distinct regulatory T cells specialized for crosstalk with epithelial environments.

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A monoclonal antibody (HML‐1) defining a novel membrane molecule present on human intestinal lymphocytes

Cited by 407 publications

References 40 publications

Phenotypical heterogeneity of CD4+CD8+ double-positive chronic T lymphoid leukemia

Phenotypical heterogeneity of CD4+CD8+ double-positive chronic T lymphoid leukemia

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

Expression of the integrin α_Eβ₇identifies unique subsets of CD25⁺as well as CD25⁻regulatory T cells

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A monoclonal antibody (HML‐1) defining a novel membrane molecule present on human intestinal lymphocytes

Cited by 407 publications

References 40 publications

Phenotypical heterogeneity of CD4+CD8+ double-positive chronic T lymphoid leukemia

Phenotypical heterogeneity of CD4+CD8+ double-positive chronic T lymphoid leukemia

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

Expression of the integrin αEβ7identifies unique subsets of CD25+as well as CD25−regulatory T cells

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Expression of the integrin α_Eβ₇identifies unique subsets of CD25⁺as well as CD25⁻regulatory T cells