Lethal vaccinia infection in cyclophosphamide-suppressed mice is associated with decreased expression of Thy-1, Lyt-2 and L3T4 and diminished IL-2 production in surviving T cells.
Prior treatment of C57BL/6J mice with 300 mg/kg of cyclophosphamide (Cy) converts a subclinical infection with vaccinia virus to a lethal disease. This is accompanied by a loss of more than 80% of spleen cells and a decreased capacity, on a cell-for-cell basis, to develop virus-immune cytotoxic T lymphocytes (CTL), although the frequency of CTL precursors among surviving T cells is not greatly modified. Phenotypically, the surviving T cells express low levels of cell-surface Thy-1, Lyt-2 and L3T4 and, upon stimulation, are less able to produce IL-2 for more than 1 week following Cy treatment. The defect in capacity to generate CTL effectors both in vitro and in vivo can be corrected by providing an exogenous source of IL-2. These experiments indicate that a single dose of Cy induces changes in T cells that persist throughout the development of an immune response. Such effects are in accordance with the known property of Cy to mediate DNA damage.
D000818:Animals; D000950:Antigens, Ly / Q000032:analysis; D000954:Antigens, Surface / Q000032:analysis*; D002478:Cells, Cultured; D003520:Cyclophosphamide / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D007108:Immune Tolerance / Q000187:drug effects*; D007376:Interleukin-2 / Q000096:biosynthesis*; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018800:Thy-1 Antigens; D014615:Vaccinia / Q000276:immunology*
D000950:Antigens, Ly; D000954:Antigens, Surface; D007376:Interleukin-2; D018800:Thy-1 Antigens; D003520:Cyclophosphamide