The mucosal T cell integrin αM290β7 recognizes a ligand on mucosal epithelial cell lines

The integrin αM290β7 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 αM290 or β7 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 Tcell 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‐a and interferon‐γ 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 αM290β7 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.

[1]  M. Haury,et al.  Intestinal T lymphocytes in the chicken express an integrin‐like antigen , 1993, European journal of immunology.

[2]  R. Jasman,et al.  Cloning and characterization of a new intercellular adhesion molecule ICAM-R , 1992, Nature.

[3]  D. Mason,et al.  Molecular cloning of ICAM-3, a third ligand for LFA-1, constitutively expressed on resting leukocytes , 1992, Nature.

[4]  F. Sánchez‐Madrid,et al.  Functional role of α2/β1 and α4/β1 integrins in leukocyte intercellular adhesion induced through the common β1 subunit , 1992 .

[5]  Xiaoping Du,et al.  Inside-out integrin signalling , 1992, Current Biology.

[6]  J. Watson,et al.  The gene organization of the human β7 subunit, the common β subunit of the leukocyte integrins HML-1 and LPAM-1 , 1992 .

[7]  M. C. Hu,et al.  Cloning and expression of mouse integrin beta p(beta 7): a functional role in Peyer's patch-specific lymphocyte homing. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[8]  P. Krajči,et al.  Expression and Regulation of Adhesion Molecules ICAM‐1 (CD54) and LFA‐3 (CD58) in Human Intestinal Epithelial Cell Lines , 1992, Scandinavian journal of immunology.

[9]  J. Watson,et al.  Molecular cloning of the mouse integrin beta 7 subunit. , 1992, The Journal of biological chemistry.

[10]  Richard O. Hynes,et al.  Integrins: Versatility, modulation, and signaling in cell adhesion , 1992, Cell.

[11]  E. Butcher,et al.  Role of integrin alpha 4 beta 7/alpha 4 beta P in lymphocyte adherence to fibronectin and VCAM-1 and in homotypic cell clustering , 1992, The Journal of cell biology.

[12]  M. Brenner,et al.  A family of beta 7 integrins on human mucosal lymphocytes. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[13]  N. Cerf-Bensussan,et al.  The human intraepithelial lymphocyte marker HML‐1 is an integrin consisting of a β7 subunit associated with a distinctive α chain , 1992 .

[14]  I. Weissman,et al.  Cloning and expression of cDNAs for the alpha subunit of the murine lymphocyte-Peyer's patch adhesion molecule , 1991, The Journal of cell biology.

[15]  P. Kilshaw,et al.  Expression and regulation of β7(βp) integrins on mouse lymphocytes: Relevance to the mucosal immune system , 1991 .

[16]  P. Howdle,et al.  Expression of the LFA‐1 β2 Integrin (CD11a/CD18) and ICAM‐1 (CD54) in Normal and Coeliac Small Bowel Mucosa , 1991, Scandinavian journal of immunology.

[17]  H. Stein,et al.  Ber-ACT8: new monoclonal antibody to the mucosa lymphocyte antigen. , 1991, Journal of clinical pathology.

[18]  T. Springer,et al.  Characterization of ICAM-2 and evidence for a third counter-receptor for LFA-1 , 1991, The Journal of experimental medicine.

[19]  D. Sheppard,et al.  Complete amino acid sequence of an integrin beta subunit (beta 7) identified in leukocytes. , 1991, The Journal of biological chemistry.

[20]  J. Watson,et al.  Cloning and sequence analysis of a novel beta 2-related integrin transcript from T lymphocytes: homology of integrin cysteine-rich repeats to domain III of laminin B chains. , 1990, International immunology.

[21]  A. Jarry,et al.  Human intestinal intraepithelial lymphocytes, a distinct population of activated T cells , 1991, Immunologic research.

[22]  P. Kilshaw,et al.  A new surface antigen on intraepithelial lymphocytes in the intestine , 1990, European journal of immunology.

[23]  T. Macdonald,et al.  Cytotoxic α/β+ and γ/δ+ T cells in murine intestinal epithelium , 1990 .

[24]  A. Bernard,et al.  Suppressor effects and cyclic AMP accumulation by the CD29 molecule of CD4+ lymphocytes , 1989, Nature.

[25]  J. Spencer,et al.  Evidence that activated mucosal T cells play a role in the pathogenesis of enteropathy in human small intestine , 1988, The Journal of experimental medicine.

[26]  C. Griscelli,et al.  A monoclonal antibody (HML‐1) defining a novel membrane molecule present on human intestinal lymphocytes , 1987, European journal of immunology.

[27]  F. Sánchez‐Madrid,et al.  LFA‐1 and Lyt‐2,3, Molecules Associated with T Lymphocyte‐Mediated Killing; and Mac‐1, an LFA‐1 Homologue Associated with Complement Receptor Function 1 , 1982, Immunological reviews.

[28]  G. Lepage,et al.  Growth characteristics and drug responses of a murine lung carcinoma in vitro and in vivo. , 1978, Cancer research.

[29]  L. M. Franks,et al.  A cell line from an induced carcinoma of mouse rectum , 1978, The Journal of pathology.

[30]  P. Riddle,et al.  Metastasizing tumors from serum-supplemented and serum-free cell lines from a C57BL mouse lung tumor. , 1976, Cancer research.