A POTENTIAL MECHANISM OF ACTION OF AN ANTIBODY (HIS45) WHICH HAS BEENSHOWN TO INDUCE PROLONGED GRAFT-SURVIVAL

Animals treated with the antibody HIS45 According to a regimen known t o prolong the survival of allogeneic skin grafts (1), show no signific ant decrease in alpha beta(+) T cells from their lymph nodes and no dr amatic change in the levels of either alpha beta(+)CD4(+) or alpha bet a(+)CD8(+) cells compared with untreated controls. However, the T cell s of treated animals showed reduced expression of the alpha beta form of the T cell receptor. Although treatment did not lead to an upregula tion of the CD25 molecule on the rat cells, treatment does lead to a r eduction at the cell surface in the amount of the determinant recogniz ed by HIS45. lit vitro analysis revealed that the HIS45 determinant wa s lost from T cells following their activation but re-expressed later. The T cells in treated animals may be partially activated. This abili ty of HIS45 to partially activate cells was supported by experiments w hich revealed that the antibody HIS45 was only weakly mitogenic in vit ro, but when present in conjunction with another stimulus such as anti -V beta cell receptor antibody or a mitogen or a superantigen, the HIS 45 antibody was shown to produce significantly increased proliferation . Functional analysis of cells from treated animals showed they respon d significantly less well in vitro to either superantigen (TSST-1) or alloantigen, compared to cells from age and sex matched untreated cont rols. Since no T cell depletion occurred following treatment the reduc ed functional ability of these cells must have been due to a functiona l defect in their ability to respond. The results suggest thar HIS45 w as having its immunosuppresive effect by delivering an incomplete acti vation signal to T cells leading to a state of anergy.