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 appearance in serum of extracellular antigen-specific T cell proteins (TABM) that are specific for the AC-injected antigen. In contrast, delayed-type 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 the eye. Because cyclophosphamide (CY) exerts selective effects on immunoregulatory T cells and macrophages, we sought to determine its effects on the appearance in serum of TNP-specific TABM in mice following intracameral injection with TNP murine spleen cells followed by epicutaneous sensitization and challenge with picrylchloride. Injection of 200 mg/kg CY 2 days before AC injection of TNP spleen cells, sensitization, and challenge prevented the suppression of DTH and the production of TNP-specific TABM. The production of TNP-specific immunoglobulins was not affected. Injection of a low dose of 20 mg/kg CY enhanced DTH 100-300% in control animals, but did not prevent either ACAID or the production of TABM. These results provide further evidence that serum TABM may be a serologic indicator of T lymphocyte activity in ACAID and that ACAID is mediated by cells sensitive to high-dose CY.
Wang
Y
Y
Department of Pathology, University of Connecticut Health Center, Farmington 06030-3105, USA.
O'Rourke
J
J
Cone
R E
RE
D000818:Animals; D000867:Anterior Chamber / Q000276:immunology*; D003520:Cyclophosphamide / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007108:Immune Tolerance / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011817:Rabbits; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis*; D013154:Spleen / Q000378:metabolism; D014301:Trinitrobenzenes / Q000276:immunology
D007166:Immunosuppressive Agents; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014301:Trinitrobenzenes; D003520:Cyclophosphamide