THYMIC HUMORAL FACTOR, THF-GAMMA-2, ENHANCES IMMUNOTHERAPY OF MURINE CYTOMEGALOVIRUS (MCMV) INFECTION BY BOTH CD4(-CELLS() AND CD8(+) IMMUNE T)

Infection of mice with murine cytomegalovirus (CMV) presents a model f or the study of the role of the immune system in the pathogenesis of h uman CMV. The contribution of the different spleen cell subsets in con ferring curative immunocytotherapy to fatally MCMV-infected immunosupp ressed mice was assessed using adoptive immunotherapy. It was found th at the efficacy of passively transferred immune spleen cells is dose d ependent and that the therapeutic effect can be enhanced considerably by treating donor mice with thymic humoral factor (THF-gamma 2). Polym erase chain reaction (PCR) of the donor spleen population was negative , indicating that no MCMV-DNA was transferred with the immune cells. A nalysis of the donor mice after THF-gamma 2 treatment showed increased levels of CMV-neutralizing antibodies, while enhancement of natural k iller (NK) activity was transient and lasted only during the early pha se of the infection. FACS analysis demonstrated that treatment with TH F-gamma 2 restored the size of both cell subsets CD4(+) and CD8(+) tha t were decreased following MCMV infection. It is shown that both CD4() and CD8(+) T-cell subsets participate in controlling the development of the fatal disease in MCMV-infected immunosuppressed recipients. It is suggested that the enhancement of the immunocompetence of both pop ulations of spleen cells from treated donors is mediated in part by th e restoration of Interleukin-2 (IL-2) production by THF-gamma 2.