Nature Biotechnology
15, 759 - 762 (1997)
doi:10.1038/nbt0897-759
Blockade of CD2-LFA-3 interactions protects human skin allografts in immunodeficient mouse/human chimerasParvez Sultan1, Jeffrey S. Schechner1, Jennifer M. McNiff1, Paula S. Hochman2, Christopher C.W. Hughes, Marc I. Lorber1, Philip W. Askenase1
& Jordan S. Pober*
1Molecular Cardiobiology Program and Departments of Biology,Dermatology, Pathology, Medicine, and Surgery, Yale University School of Medicine, New Haven, CT 06536.
2Biogen, Inc., Cambridge, Massachusetts, 02142. Department of Molecular Biology and Biochemistry, University of California at Irvine, CA 92697.
*e-mail: jordan_pober@quickmail.yale.edu. A human skin allograft injury model in immunodeficient mice, engrafted with human peripheral blood mononuolear cells from a different donor, has been used to test whether reagents that block human T cell CD2 Interactions with its principal ligand, LFA-3 (CD58), can inhibit immune reactions in vivo. In this model, human skin grafts show a reproducible pattern of progressive human T-cell infiltration and human graft microvascular injury that resembles human first-set skin graft rejection. Murine Mab to human LFA-3 or human LFA-3-lgG1 fusion protein, but not isotype-matched control antibodies, each markedly protected skin grafts from leukocyte infiltration and injury. These data provide the first evidence that LFA-3 functions in vivo and establish the ability of this new model to test human-specific immune modulators.
REFERENCES
- Pober, J.S., Orosz, C.G., Rose, M.L., and Savage, C.O.S. 1996. Can graft endothelial cells initiate a host anti-graft immune responses? Transplantation 61: 343−349. | Article | PubMed | ISI | ChemPort |
- Murray, A.G., Khodadoust, M.M., Pober, J.S., and Bothwell, A.L.M. 1994. Porcine aortic endothelial cells strongly activate human T cells: direct presentation of swine MHC antigens and effective costimulation by swine ligands for human CD2 and CD28. Immunity 1: 57−63. | Article | PubMed | ISI | ChemPort |
- Sanchez-Madrid, F., Krensky, A.M., Ware, C.F., Robbin, E., Strominger, J.L., Burakoff, S.J., and Springer, T.A. 1982. Three distinct antigens associated with human T-lymphocyte-mediated cytolysis: LFA-1, LFA-2 and LFA-3. Proc. Natl. Acad. Sci. USA 79: 7489−7493. | PubMed | ChemPort |
- Collins, T., Krensky, A.M., Clayberger, C., Fiers, W., Gimbrone, M.A. Jr., Burakoff, S.J., and Pober, J.S. 1984. Human cytolytic T lymphocyte interactions with vascular endothelium and fibroblasts. J. Immunol. 133: 7878−1884.
- Shaw, S., Ginther Luce, G.E., Quinones, R., Gress, R.L., Springer, T.A., and Sanders, M.E. 1986. Two antigen-independent adhesion pathways used by human cytotoxic T-cell clones. Nature 323: 262−264. | PubMed | ISI | ChemPort |
- van Kooyk, Y., van de Wiel-van Kemenade, P., Weder, P., Kuijpers, T.W., and Figdor, C.G. 1989. Enhancement of LFA-1-mediated cell adhesion by triggering through CD2 or CDS on T lymphocytes. Nature 342: 811−813. | Article | PubMed | ChemPort |
- Kato, K., Koyanagi, M., Okada, H., Takanishi, T., Wong, Y.W., Williams, A.F., et al. 1992. CD48 is a counter-receptor for mouse CD2 and is involved in T cell activation. J. Exp. Mad. 176: 1241−1249 | ChemPort |
- Murray, A.G., Petzelbauer, P., Hughes, C.C.W., Costa, J., Askenase, P., and Pober, J.S. 1994. Human T cell-mediated destruction of allogeneic dermal microvessels in a SCID mouse. Proc. Natl. Acad. Sci. USA 91: 9146−9150 | ChemPort |
- Majeau, G.R., Meier, W., Jimmo, B., Kioussis, D., and Hochman, P.S. 1994. The mechanism of LFA-3-lg inhibition of T cell responses: structure/function analysis in vitro and in human CD2 transgenic mice. J. Immunol. 152: 2753−2767. | PubMed | ISI | ChemPort |
- Kaplon, R.J., Hochman, P.S., Michler, R.E., Kwiatkowski, P.A., Edwards, N.M., Berger, C.L., et al. 1996. Short course single agent therapy with an LFA-3-lgG, fusion protein prolongs primate cardiac allograft survival. Transplantation 61: 356−363. | Article | PubMed | ISI | ChemPort |
- Chisholm, P.L., Williams, C.A., Jones, W.E., Majeau, G.R., Oleson, F.B., Burrus-Fischer, B., et al. 1994. The effects of an immunomodulatory LFA3 IgGl function protein on non-human primates. Therapeutic Immunology 1: 205−276. | PubMed | ChemPort |
- Miller, G.T., Hochman, P.S., Meier, W., Tizard, R., Bixler, S.A., Rosa, M.D., and Wallner, B.P. 1993. Specific interaction of lymphocyte function associated antigen 3 with CD2 can inhibit T cell responses. J. Exp. Med. 178: 277−222.
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