HIGH-DOSE CYCLOPHOSPHAMIDE INHIBITS ANTERIOR CHAMBER-ASSOCIATED IMMUNE DEVIATION (ACAID) AND THE PRODUCTION OF EXTRACELLULAR ANTIGEN-SPECIFIC T-CELL PROTEINS INDUCED BY TRINITROPHENYLATED (TNP) SPLEEN-CELLS

Injection of antigen into the anterior chamber (AC) of the eye induces the production of IgM and IgG1 antibodies and potentiates the appeara nce in serum of extracellular antigen-specific T cell proteins (TABM) that are specific for the AC-injected antigen. In contrast, delayed-ty pe hypersensitivity (DTH) to the injected antigen is suppressed. This manifestation of anterior chamber-associated immune deviation (ACAID) is believed to be a key part of the basis of the immune privilege of t he eye. Because cyclophosphamide (CY) exerts selective effects on immu noregulatory T cells and macrophages, we sought to determine its effec ts on the appearance in serum of TNP-specific TABM in mice following i ntracameral injection with TNP murine spleen cells followed by epicuta neous sensitization and challenge with picrylchloride. Injection of 20 0 mg/kg CY 2 days before AC injection of TNP spleen cells, sensitizati on, and challenge prevented the suppression of DTH and the production of TNP-specific TABM. The production of TNP-specific immunoglobulins w as not affected. Injection of a low dose of 20 mg/kg CY enhanced DTH 1 00-300% in control animals, but did not prevent either ACAID or the pr oduction of TABM. These results provide further evidence that serum TA BM may be a serologic indicator of T lymphocyte activity in ACAID and that ACAID is mediated by cells sensitive to high-dose CY. (C) 1995 ac ademic Press, Inc.