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The Suppressive Effect of Immunization on the Proliferative Responses of Rat T Cells in Vitro

II. Abrogation of Antigen-Induced Suppression by Selective Cytotoxic Agents¹

From the Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06510

Abstract

Rats given large i.v. doses of ovalbumin or sheep erythrocytes manifest suppressed spleen cell responses (³H-thymidine incorporation) to PHA within hours. Removal of glass wool-adherent cells totally restores responsiveness to that of normal nonadherent spleen cell cultures. Carrageenan, selectively toxic for macrophages, partially restores responses of antigen-suppressed spleen cells in culture, suggesting a supportive role for macrophages in the suppression phenomenon. Treatment of donors with low doses of cyclophosphamide (20 to 50 mg/kg) at the time of antigen injection abrogates the ability of their spleen cells to suppress the responses of normal cells to PHA. The low dose of cyclophosphamide required indicates a target other than the B cell or macrophage and suggests the possibility that cyclophosphamide eliminates the suppressor T cell component of the macrophage-T cell complex.

Footnotes

¹ This work was supported by United States Public Health Service Grants AI-06112 and AI-06455 and Contract CB-43926.

² Postdoctoral Trainee, National Institutes of Health Grant AI-291-09S1. Present address: Department of Microbiology, University of Cincinnati Medical Center, Cincinnati, Ohio 45219.