Emergence of a radioresistant population of co-stimulatory splenocytes during remission of experimental autoimmune encephalomyelitis in Lewis rats.

T-cell hybridomas specific for myelin basic protein (MBP) were used to assess regulation of co-stimulatory signals during remission of experimental autoimmune encephalomyelitis (EAE) in Lewis rats. Both THYB-1 and THYB-2 subsets of T-cell hybridomas recognize class II major histocompatibility complex-restricted determinants in the 72-86 encephalitogenic region of MBP. However, THYB-2 hybrids uniquely express additional requirements for co-stimulatory signals from radiosensitive splenocytes (SPL) to support the response of MBP-stimulated IL-2 production. Hence, this subset provides a means to study regulation of THYB-2 specific co-stimulatory signals during the course of EAE. This study revealed that sensitization of Lewis rats with MBP in complete Freund's adjuvant induced a radioresistant subpopulation of co-stimulatory SPL that emerged during the remission phase of EAE. These radioresistant SPL provided specific accessory cell activities that fulfilled the co-stimulatory requirements of THYB-2 hybrids. These findings support the hypothesis that in vivo activation events elicit radioresistance in an emergent clonally expanding population of antigen-specific lymphocytes. A central prediction of this hypothesis is that cellular activation should confer radioresistance to co-stimulatory lymphocytes. This prediction was verified by the observation that in vitro activation of naive SPL with different B- and T-cell mitogens conferred radioresistance to co-stimulatory SPL. Mitogenic activation not only induced radioresistance but also dramatically augmented co-stimulatory activity of purified B cells. In summary, the results of this study support the hypothesis that in vivo activation of co-stimulatory lymphocytes may regulate activities of encephalitogenic T-helper cells during progression and remission of EAE.