Antioligodendrocyte Autoreactive T Cells

Summary

We have investigated the role of oligodendrocytes (OD), the glial cells that produce the myelin sheath in the central nervous system (CNS), as possible targets for T-cell mediated autoimmune demyelinating processes.

In a first set of experiments, lymph node cells (LNC) from SJL/J mice immunized with either rat whole spinal cord (WSC) homogenate or myelin basic protein (BP) in the presence of complete Freund’s adjuvant (CFA) were assayed for their in vitro proliferative response to BP and to purified OD. WSC-immunized mice displayed a strong and persistent response to both syngeneic and rat OD, and a much weaker response to rat BP. Moreover LNC from BP-immunized mice showed a small response to BP, but no response to OD, indicating that OD are not able to present their endogeneous BP to lymphocytes. These data suggest that autoreactive T cells, specific for OD antigens other than BP, had been stimulated by WSC-immunization.

To further characterize these T cells, a second set of experiments was undertaken, where normal SJL/J mouse splenocytes were sensitized in vitro by Lewis rat OD and maintained as long-term T cell lines in IL-2-containing medium. These lines were initially composed of a majority of CD4+ CD8− T cells and could mount a proliferative response to Lewis rat OD in the absence of IL-2. T cell lines cultured for more than 4 months included a majority of CD8+ CD4− T cells and required exogeneous IL-2 to develop a proliferative response to OD. A T cell clone of the CD8+ CD4− phenotype was obtained from these lines. The proliferative response of these lines and clones could be elicited by syngeneic OD as well as by Lewis rat OD, but appeared to be tissue-specific, since other tissues failed to trigger their proliferation, and was not MHC-restricted.

The molecular nature of the OD autoantigen recognized, and the pathogenic and/or physiologic role of these non-classical autoreactive T cells remain to be elucidated.