T‐Cell‐Mediated Immunopathology in Viral Infections

H-2 compatibility requirement for virus-specific T-cell-mediated cytolysis. Evaluation of the role of H-2I region and non-H-2 genes in regulating immune response.

“…The conclusion that Icoded structures appear to be of certainly lesser relevance than K-or D-coded structures for virus-specific T-cell effector functions is supported by the finding that the adoptive transfer of both inflammatory process (18) and anti-viral protection is also dependent upon K or D, but not/-region compatibility (30). 2 The capacity to generate D~-associated cytotoxicity in vivo was also not under However, in view of the results presented in Tables IV-VII, the low responsiveness of D2.GD and DBA/2 mice, as compared with other H-2 ~ strains like BALB/c or B10.D2, is most likely explained by the influence of genes other than those of the I-or other H-2-gene regions. Different from/r-controlled immune responses to soluble, defined antigens, low responsiveness to the WE strain of LCMV is inversely related to the infectious virus dose; high virus dose causes low responsiveness.…”

“…The low responsiveness could thus be only an apparent one and mainly due to an ~'adsorption" or "competition" phenomenon. LCMV is by itself not or only rarely cytopathogenic, and pathological processes are thus not generally caused by the virus itself (1)(2)(3). Extensive viral replication during a generalized infection could thus result in widespread tissue distribution of infected cells expressing LCMV-altered H-2K or D. Cytotoxic T cells could thus be '~competed fo~' elsewhere in liver and other organs, or in spleens in mice containing many infected cells; such a mechanism (2) may well be the basis of the high dose immune paralysis phenomenon described by Hotchin (1) for acute LCM.…”

“…The experimental evidence leading to this conclusion has been reviewed in extenso recently (1)(2)(3). The pathological process in vivo can be monitored in vitro by measuring LCM virus (LCMV)-specific cytotoxic activity of thymus-derived lymphocytes (T cells) for LCMV-infected target cells (4)(5)(6)(7).…”

“…More recently, with the mouse strains available now, this difference no longer appears to be statistically significant (10). Nevertheless, it was during the attempt to correlate increased susceptibility to acute LCM with the capacity of various mouse strains to generate LCMV-specific T cells with greater cytotoxic activity and quicker than less susceptible mice that the unexpected H-2 restriction of cytolytic activity was originally found (2,11).…”

Cellular Immune Recognition and the Biological Role of Major Transplantation Antigens

“…These findings separated the MHC-restricted recognition by virus-specific cytotoxic T-cells from the MHC class II -(H-2I)-linked immune response phenomena regulating T-cell-B-cell, or T-cell-macrophage interactions. Analyses of cytotoxic T-cell interactions in vivo causing lethal immunopathology [57], antiviral protection [58], and protection against Listeria monocytogenes [59], all confirmed that MHC restriction was also valid in vivo.…”