A potential mechanism of action of an antibody (HIS45) which has been shown to induce prolonged graft survival.
Animals treated with the antibody HIS45 According to a regimen known to prolong the survival of allogenic skin grafts (1), show no significant decrease in alpha beta + T cells from their lymph nodes and no dramatic change in the levels of either alpha beta + CD4+ or alpha beta + CD8+ cells compared with untreated controls. However, the T cells of treated animals showed reduced expression of the alpha beta form of the T cell receptor. Although treatment did not lead to an upregulation of the CD25 molecule on the rat cells, treatment does lead to a reduction at the cell surface in the amount of the determinant recognized by HIS45. In vitro analysis revealed that the HIS45 determinant was lost from T cells following their activation but re-expressed later. The T cells in treated animals may be partially activated. This ability of HIS45 to partially activate cell was supported by experiments which revealed that the antibody HIS45 was only weakly mitogenic in vitro, but when present in conjunction with another stimulus such as anti-V beta cell receptor antibody or a mitogen or a superantigen, the HIS45 antibody was shown to produce significantly increased proliferation. Functional analysis of cells from treated animals showed they respond significantly less well in vitro to either superantigen (TSST-1) or alloantigen, compared to cells from age and sex matched untreated controls. Since no T cell depletion occurred following treatment the reduced functional ability of these cells must have been due to a functional defect in their ability to respond. The results suggest that HIS45 was having its immunosuppressive effect by delivering an incomplete activation signal to T cells leading to a state of anergy.
Aspinall
R
R
Department of Immunology, Chelsea and Westminster Hospital, Charing Cross and Westminster Medical School, London, England.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001427:Bacterial Toxins; D002478:Cells, Cultured; D004768:Enterotoxins / Q000276:immunology; D005260:Female; D006085:Graft Survival / Q000276:immunology*; D016130:Immunophenotyping; D008198:Lymph Nodes / Q000166:cytology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology; D018089:Superantigens / Q000276:immunology
D000911:Antibodies, Monoclonal; D001427:Bacterial Toxins; D004768:Enterotoxins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal