FUNCTIONAL HETEROGENEITY OF LYMPHOCYTEC CHORIOMENINGITIS VIRUS-SPECIFIC T LYMPHOCYTES I. Identification of Effector and Memory Subsets*

Infections produced in adult mice by the neurotropic Armstrong strain of lymphocytic choriomeningitis (LCM) ' virus can result in either of two contrasting outcomes, each of which depends on the route of virus administration. Inoculated intracerebrally (i.c.), any dose of infectious virus replicates predominantly in neural membranes, with little or no extension to parenchymal cells of the central nervous system (CNS) and with minimal involvement of extraneural tissues (1, 2). Although the infection is noncytopathic, an acute uniformly fatal CNS disease develops as a direct result of virus-induced immune-mediated damage to infected cells of the leptomeninges, choroid plexus, andependyma (1, 3). Convincing evidence for the immunopathological nature of LCM comes from our previous studies in which immunosuppression with cyclophosphamide (CY) after cerebral infection was shown to prevent the development of CNS disease and to subsequently lead to the development of a chronic asymptomatic virus-carrier state (l, 4). In contrast, mice given LCM virus by an extraneural route develop a self-limiting subclinical infection confined to extraneural tissues and which eventually confers a solid protective immunity to a second challenge of virus given i.c. (5). However, under appropriate conditions