Differential effect of hybrid resistance on the localization of virus-immune effector T cells to spleen and brain.
The hybrid resistance (Hr) effect operates in the lymphocytic choriomeningitis (LCM) in vivo transfer model to inhibit both the level of cytotoxicity T lymphocyte (CTL) generation in spleen and the induction of inflammation in cerebrospinal fluid (CSF). The effect is seen when LCM virus-immune T cells that are homozygous for H-2Db are injected into virus-infected, immunosuppressed recipients that are heterozygous for this allele, or into radiation chimeras that express an appropriate F1 phenotype. Evidence that Hr to T-cell transfer is cell-dose-dependent and tends to diminish with age was found in both chimeric and normal F1 mice. Inhibition of the capacity of injected T cells to cause meningitis is a more sensitive measure of Hr than is the further stimulation of CTL effectors in recipient lymphoid tissue. The injection of large numbers of H-2b virus-immune T cells into (H-2k X H-2bF1----H-2k) virus-infected recipients did not induce any cellular extravasation into CSF, though potent H-2b-restricted CTL effectors were generated in recipient spleen. Evidence of minimal inflammatory process was found in one experiment where these chimeras were given a comparable dose of (H-2b X H-2d)F1 immune spleen cells. Development of this T-cell-mediated immunopathological process depends essentially on the expression of the appropriate H-2 restriction element on radiation-resistant host cells which, in this case, presumably constitute part of the physiological barrier between blood and CSF.