Effects of anti-interleukin-2 receptor antibody and cyclosporin A on human T cell proliferation in primary mixed lymphocyte reaction.
Effects of anti-IL2 receptor antibody (anti-IL2 RAb) and cyclosporin A (CsA) on human T cell proliferation in primary mixed lymphocyte reaction (MLR) were investigated. Both agents inhibited the proliferative response induced by alloantigen in a dose dependent manner when they were added at the initiation of culture. We also analyzed the expression of activation antigen on responder cells and the kinetics of T lymphocyte subset proliferation during MLR using two-color flow cytometry. Cells expressing activation antigens, such as IL-2 receptor and HLA-DR, were found less frequently in anti-IL2 RAb-treated MLR culture (4.8%) than in CsA-treated MLR culture (16.5%) on day 6. Furthermore, proliferation of CD8+CD11- cells, considered a cytotoxic T cell subset, were inhibited significantly more in anti-IL2 RAb-treated MLR culture than in CsA-treated MLR culture. We further demonstrate that CsA inhibits preferentially IL-2 production and anti-IL2 RAb inhibits T cell proliferation by blocking an absorption of IL-2 by activated lymphocytes. These data suggest that anti-IL2 RAb selectively inhibits alloantigen-activated T cells and may prove to be of significant value as an immunosuppressive agent in clinical organ transplantation.
Oiwa
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K
Sakagami
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Orita
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K
D000906:Antibodies; D003524:Cyclosporins / Q000494:pharmacology; D006684:HLA-DR Antigens; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed; D015375:Receptors, Interleukin-2 / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D000906:Antibodies; D003524:Cyclosporins; D006684:HLA-DR Antigens; D015375:Receptors, Interleukin-2