At varying intervals after immunizing infections of adult BALB/c mice with lymphocytic choriomeningitis (LCM) virus, splenic lymphocytes were tested for their ability to either elicit acute LCM or protect against lethal intracerebral LCM virus challenge when transferred to syngeneic recipients that were, respectively, virus carriers induced by cyclophosphamide-induced immunosuppression and normal susceptible mice. These lymphocytes were also assayed for their capacity to lyse, in vitro, LCM virus-infected BALB 3T3 cells labeled with 51Cr. Only lymphocytes obtained from donor mice between 6 and 8 days postimmunization significantly protected normal recipients from the development of lethal central nervous system (CNS) disease when transferred 18-24 h before virus challenge. At 10 days they were not protective even though their cytolytic activity in vitro either exceeded or approximated that of protective lymphocytes. The capacity to protect more closely corresponded with a period of virus-induced DNA synthesis in donor spleens as measured by the incorporation of [5--125I]-2'-DEOXYURIDINe. However, none of these cytolytically active lymphocyte populations were effective in mediating acute CNS disease when transferred to virus-carrier mice. In contrast, lymphocytes obtained 18 days or later after primary immunization, although having no protective capacity and exhibiting minimal cytolytic activity in vitro, were able to regularly produce acute disease in virus-carrier mice. The ablation by anti-theta-serum treatment of these in vivo and in vitro virus-specific immune functions established that the relevant lymphoid cells were T lymphocytes. Similarly, reconstitution of C3H times C57BL F1 adult mice, depleted of lymphocytes by thymectomy and lethal irradiation, with syngeneic day 8 immune donor lymphocytes rendered them resistant to the development of the carrier state after intracerebral virus challenge; reconstitution of such animals with nonimmune lymphocytes restored their ability to develop typical LCM. Collectively, these data indicate that immunogenic stimulation with LCM virus leads to the development of at least two different virus-specific T-lymphocyte subsets: (a) an early appearing transient effector population of cells and, perhaps, their immediate precursors whose generation requires the presence of virus, and (b) a stable memory population that appears well after virus clearance and which has little or not no cytolytic activity. The possible mechanism by which these functionally different subsets can influence the outcome of acute or chronic LCM virus infections is discussed.

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