The mucosal T cell integrin α_M290β7 recognizes a ligand on mucosal epithelial cell lines

Abstract

The integrin alpha M290 beta 7 is expressed at high levels on mucosal T cells, particularly on those within the epithelium of the gut. We now report that a mouse T cell hybridoma, MTC-1, with similar surface expression of this molecule, adhered strongly to cells of the mouse rectal carcinoma line CMT93 and that adhesion was blocked completely by the monoclonal antibody (mAb) M290. Other mAb to the alpha M290 or beta 7 subunits had little or no inhibitory effect. M290 also inhibited adhesion of the hybridoma to cells of the mouse lung carcinomas CTM64/61 and KLN205 but had little or no effect on adhesion to seven other mouse epithelial cell lines or to the human colon carcinoma line, HT29. Intraepithelial lymphocytes (IEL) isolated from the small intestine of BALB/c mice displayed potent T cell receptor-dependent cytotoxic effector function against CMT93 in the presence of low concentrations of Phytolacca americana lectin. This cytotoxic activity also was inhibited by the M290 mAb. Treatment of CMT93 cells with tumor necrosis factor-alpha and interferon-gamma induced expression de novo of ICAM-1 and reduced the inhibitory effect of M290 in tests both for adhesion and cytotoxicity. In further experiments cytotoxic activity of IEL against the mastocytoma P815 was investigated. This target cell was considered not to possess a ligand for the integrin. In this case cytotoxic effector function was triggered by anti-CD3 mAb and, in contrast to results with CMT93, target cell lysis was increased in the presence of M290 and other antibodies to the integrin, suggesting a co-stimulatory effect. These results show that alpha M290 beta 7 recognizes a ligand on the surface of certain epithelial cell lines. Further, they provide the first clear indication that this integrin may play an important role in functional interactions between T cells and the mucosal epithelium.

Post-Transplant Renal Tubulitis: The Recruitment, Differentiation and Persistence of Intra-Epithelial T Cells

“…Crucially, it was shown that the cytotoxic function of these cells for renal epithelial cells was inhibited by antibody blockade of CD103, a treatment that also inhibits adhesion to the target cells. These results are consistent with earlier studies that show that the lysis of some cancer cell lines by gut-derived intraepithelial lymphocytes could be inhibited by blockade of CD103 (62). The concept that selective adhesion to epithelium can provide a basis for tissue-specific damage during tubulitis was reinforced by the observation that induction of the aEb7 integrin is associated with diminished expression of the adhesion molecule LFA-1 (aLb2 integrin) (63).…”

Targeting LFA-1 and CD154 Suppresses the In Vivo Activation and Development of Cytolytic (CD4-Independent) CD8+ T Cells

“…A and C, After 60 days (n ϭ 5, black lines) or 100 days (n ϭ 3, grey lines) of stable hepatocyte function, five recipients with long-term function received adoptive transfer of 2 ϫ 10 6 naive CD8 ϩ T cells. Two mice died of causes unrelated to transplan-in providing costimulation for CD8 ϩ T cell proliferation and cytolytic effector function (53). Combined blockade of CD40/CD154 costimulation and LFA-1-mediated signaling prevented up-regulation of CD103 expression on CD8 ϩ LICs (Fig.…”

T cell adhesion and cytolysis of pancreatic cancer cells: a role for E-cadherin in immunotherapy?

“…T-cell-mediated target cell lysis can be modelled in the absence of a specific antigen by re-stimulating activated T cells with CD3 antibodies immediately prior to 51 Cr-release assay (Roberts and Kilshaw, 1993). This 're-directed lysis' technique was used in the current study to assess specific cytolysis of Panc-1 cells using Experimental Therapeutics MLR-activated T cells as an effecter cell population.…”

“…It has also been demonstrated that the aEb7 integrin, in common with LFA-1, may have co-stimulatory properties (Sillett et al, 1999). For example, IEL-mediated cytolysis is enhanced via an unknown intracellular signalling pathway if the aEb7 integrin is cross-linked with antibody (Roberts and Kilshaw, 1993). Furthermore, IEL have a greater capacity than peripheral blood lymphocytes (PBL) for spontaneous cytotoxicity of epithelial cells (Taunk et al, 1992).…”