The presence of infectious virus but not conventional antigen can exacerbate graft-versus-host reactions.
Previous reports have demonstrated that the introduction of virus (MCMV, HSV-1) concurrent with a graft-versus-host reaction (GvHR) limited to a class I MHC disparity can result in the enhancement of GvHR-associated phenotypic (changes in CD4/CD8 ratio) and functional (inability to produce secondary antibody responses) alterations including the augmentation of in situ natural killer (NK) and donor anti-host cytotoxic T-cell activity. In the present study, we investigated whether immunogens other than infectious virus may be capable of enhancing GvHR. Mice receiving donor cells and the T-dependent antigen dinitrophenyl-bovine serum albumin (DNP-BSA) did not display exacerbated GvHR as evidenced by the absence of phenotypic alterations and the absence of elevated NK activity and the lack of donor anti-host cytotoxic activity. Furthermore, these recipients produced normal levels of IgM and IgG anti-DNP antibody. In addition, mice which received ultraviolet light (UV)-inactivated virus (even at 100 x dosage) together with donor cells also did not exhibit exacerbated GvHR. In total, these findings illustrate a novel ability of infectious virus to exacerbate GvH reactions and are consistent with the hypothesis that viral-induced immune responses may be important in the ability of a pathogen to induce the development of severe GvHR.
Cray
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Department of Microbiology and Immunology, University of Miami School of Medicine, Florida 33101.
Levy
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D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003587:Cytomegalovirus / Q000276:immunology* / Q000528:radiation effects; D003601:Cytotoxicity Tests, Immunologic; D004140:Dinitrophenols / Q000276:immunology*; D006087:Graft vs Host Reaction / Q000276:immunology*; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology; D008221:Lymphoid Tissue / Q000637:transplantation; D051379:Mice; D008810:Mice, Inbred C57BL; D012710:Serum Albumin, Bovine / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000276:immunology
D004140:Dinitrophenols; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D014613:Vaccines, Attenuated; C034638:dinitrophenyl-bovine serum albumin; D012710:Serum Albumin, Bovine