RELATIVE SUSCEPTIBILITY OF SJL J AND B10.S MICE TO EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS (EAE) IS DETERMINED BY THE ABILITY OF PRETHYMIC CELLS IN BONE-MARROW TO DEVELOP INTO EAE EFFECTOR T-CELLS

SJL/J mice are highly susceptible to actively induced experimental allergic encephalomyelitis (EAE), whereas B10.S mice are resistant. However, both strains share the H-2s haplotype. We have previously shown that the relative susceptibility of SJL/J and BIO.S mice to acute EAE correlates, respectively, with high and low responsiveness to myelin basic protein (MBP), as determined by cloning and limiting dilution analysis of in vitro T cell proliferation. Here, we have investigated the ability of SJL/J and B10.S mice to generate EAE-effector T cells in vivo. We have developed a new mouse strain, BIO.S Thy 1.1, that differs at the Thy 1 locus from SJL/J and BIO.S mice (both Thy 1.2) but has the same MHC and resistance pattern to EAE as do BIO.S mice. Using radiation bone marrow chimeras formed between SJL/J and BIO.S Thy 1.1 mice, we have shown that a population of radiosensitive prethymic cells in SJL/J bone marrow has an intrinsic potential to generate EAE-effector T cells, whereas that in B10.S Thy 1.1 bone marrow does not. This lack of detectable EAE effector cells in BIO.S Thy 1.1 mice does not appear to be due to the generation of suppressor T cells or to a defect in antigen-presenting cells. Moreover, the potential of SJL/J bone marrow to generate EAE-effector T cells is not inhibited by the concomitant presence of BIO.S Thy 1.1 bone marrow cells, thymocytes or dendritic cells in mixed chimeras. Hence, the relative susceptibility of SJL/J and BIO.S mice to EAE appears to be directly related to the respective responder status of their T cells to MBP, as evidenced by their ability (or inability) to generate EAE-effector T cells. This high and low responder status appears in turn to be linked to non-MHC background genes, although this has not been established formally.