Inhibition of murine corneal allograft rejection by treatment with antibodies to CD80 and CD86.

The purpose of this study was to investigate the role of CD80 and CD86 costimulatory molecules in corneal allograft rejection. Anti-CD80 and anti-CD86 monoclonal antibodies (mAbs) were administered after orthotopic corneal allograft transplantation. Graft rejection was observed by biomicroscopy. Population and localization of CD80(+)and CD86(+)cells in the cornea, cervical lymph nodes, and spleen were examined by flow cytometry and immunohistochemistry. The combined use of anti-CD80 and anti-CD86 mAbs was effective in prolonging corneal allograft survival. In the untreated mice bearing rejected graft, many CD86(+)and CD80(+)cells were found around the host-graft junctional area in the cornea, and CD86(high)cells were found in the cervical lymph node and spleen. In contrast, few CD86(+)or CD80(+)cells were observed in the cornea, cervical lymph node, and spleen from the mice treated with anti-CD80/CD86 mAbs. These results demonstrated a significant role of CD80 and CD86 costimulatory molecules in corneal allograft rejection.

[1]  J. Niederkorn.  The immune privilege of corneal allografts. , 1999, Transplantation.

[2]  K. Okumura,et al.  A crucial role of host CD80 and CD86 in rat cardiac xenograft rejection in mice. , 1998, Transplantation.

[3]  M. Isobe,et al.  Specific immunosuppression of corneal allograft rejection by combination of anti-VLA-4 and anti-LFA-1 monoclonal antibodies in mice. , 1997, Experimental eye research.

[4]  Freddie H. Fu,et al.  Costimulatory molecule-deficient dendritic cell progenitors (MHC class II+, CD80dim, CD86-) prolong cardiac allograft survival in nonimmunosuppressed recipients. , 1996, Transplantation.

[5]  M. Isobe,et al.  The role of cell adhesion molecules in allograft rejection after penetrating keratoplasty in mice. Clinical and immunohistochemical study , 1996, Graefe's Archive for Clinical and Experimental Ophthalmology.

[6]  K. Okumura,et al.  The differential role of CD86 and CD80 co-stimulatory molecules in the induction and the effector phases of contact hypersensitivity. , 1996, International immunology.

[7]  P. Linsley,et al.  Long-term acceptance of skin and cardiac allografts after blocking CD40 and CD28 pathways , 1996, Nature.

[8]  K. Okumura,et al.  Specific acceptance of cardiac allografts after treatment with antibodies to CD80 and CD86 in mice. , 1996, Transplantation proceedings.

[9]  G. Freeman,et al.  Inhibition of transplant rejection following treatment with anti-B7-2 and anti-B7-1 antibodies. , 1995, Transplantation.

[10]  M. Azuma,et al.  Preferential dependence of autoantibody production in murine lupus on CD86 costimulatory molecule , 1995, European journal of immunology.

[11]  H. Yang,et al.  Prolongation of rat islet allograft survival by treatment with monoclonal antibodies against VLA-4 and LFA-1. , 1995, Transplantation.

[12]  J. Bluestone,et al.  The B7 and CD28 receptor families. , 1994, Immunology today.

[13]  J. Bromberg,et al.  Anti-CD2 receptor and anti-CD2 ligand (CD48) antibodies synergize to prolong allograft survival , 1994, The Journal of experimental medicine.

[14]  J. Streilein,et al.  ORTHOTOPIC CORNEAL TRANSPLANTATION IN MICE—EVIDENCE THAT THE IMMUNOGENETIC RULES OF REJECTION DO NOT APPLY , 1992, Transplantation.

[15]  J. Allison,et al.  CD28-mediated signalling co-stimulates murine T cells and prevents induction of anergy in T-cell clones , 1992, Nature.

[16]  M. Isobe,et al.  Specific acceptance of cardiac allograft after treatment with antibodies to ICAM-1 and LFA-1. , 1992, Science.

[17]  Timothy A. Springer,et al.  Adhesion receptors of the immune system , 1990, Nature.

[18]  R. Colvin,et al.  In vivo effects of monoclonal antibody to ICAM-1 (CD54) in nonhuman primates with renal allografts. , 1990, Journal of immunology.