It is postulated that the central immunoregulatory abnormality in multiple sclerosis (MS) is a failure to suppress the responses of helper-amplifier T cells activated either by class II major histocompatibility (MHC) antigens alone or by certain restricted classes of antigens recognized in the context of these antigens. One prediction of this hypothesis is that effector cells capable of mediating tissue damage, such as cytotoxic T cells, are generated as a result of the regulatory abnormality. In preliminary studies a failure of autologous mixed lymphocyte response (AMLR)-primed T cells in patients with active/acute MS to suppress a fresh AMLR has been identified. This contrasts with the suppression of the AMLR seen in normal individuals and in stable MS. This is a restricted abnormality of immune regulation because mixed lymphocyte response (MLR)-priming leads to the development of suppression of fresh MLR in all cases. Further, the AMLR in active/acute MS is enhanced by AMLR-primed CD4+ cells, suggesting an abnormal amplification mechanism. This apparently occurs in the presence of CD8+ suppressor cells, whose function is demonstrated in the absence of AMLR-primed CD4+ cells. The proposed research will test this hypothesis by investigating further the regulation of the AMLR in both normal individuals and in patients with multiple sclerosis as the AMLR may reflect MS events in vivo. The phenotype and function of a subset of CD4+ cells with suppressor function will be defined. Then helper- amplifier cells, which are presumably also contained within this T cell subset will be characterized. It is then proposed to investigate the functional significance of aberrant AMLR regulation by determining whether abnormal regulation leads to the generation of effector cells through increased levels of help.
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| Bell, J; Adler, M W; Greenstein, J I (1992) The effect of arginine vasopressin on the autologous mixed lymphocyte reaction. Int J Immunopharmacol 14:93-103 |
