LYMPHOKINE MESSENGER-RNA EXPRESSION IN THE SPINAL-CORDS OF LEWIS RATSWITH EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS IS ASSOCIATED WITH A HOST RECRUITED CD45R HI CD4+ POPULATION DURING RECOVERY/

To evaluate CD4+ T cell subpopulations involved in the induction and r ecovery from experimental autoimmune encephalomyelitis (EAE), the CD45 R phenotype and lymphokine mRNA profile was evaluated for encephalitog enic CD4+ T cell lines in vitro and compared to CD4+ T cells isolated from the spinal cord of Lewis rats with EAE. All of the myelin basic p rotein (MBP)-specific T cell lines and clones that adoptively transfer red EAE were > 90% CD4+ and > 90% CD45R lo. A time course of EAE disea se progression was monitored as a function of the percentage of CD45R hi/CD4+ T cells isolated from the spinal cords of diseased animals. Th e majority of CD4+ T cells found in the central nervous system during the early phase of passive EAE were CD45R lo (the same as the encephal itogenic lines/clones). A large increase of the CD45R hi/CD4+ T cells (up to 45%) was observed during the peak and recovery phases of EAE. L ymphokine mRNA production was analyzed from antigen-stimulated MBP-spe cific lines, and from spinal cord lymphocytes isolated from rats with EAE. The BP-specific lines produced Th1 lymphokines (IL-2, IFN-gamma, and TNF-alpha), while the spinal cord lymphocytes produced the same Th 1 lymphokines as well as IL-4 and IL-10. The CD45R hi/CD4+ T cells iso lated from the spinal cords were larger and expressed more lymphokine RNA per cell than the CD45R lo/CD4+ T cells. The encephalitogenic cell s (CD45R lo) were detected in the spinal cords of rats with a fluoresc ent dye and by allelic transfers and all of the CD45R hi/CD4+ T cells were found to be host recruited. Thus it appears that the CD45R hi/CD4 + lymphocytes found in the spinal cord represent a host-recruited, act ivated cellular infiltrate that increased in number in the recovery ph ase of EAE and synthesized both Th1 and Th2 lymphokines.