T cell subsets required for in vivo and in vitro responses to single and multiple minor histocompatibility antigens.
The requirement for helper T cells in the in vivo and in vitro T cell response to a diverse panel of minor histocompatibility antigens in mice was investigated. Target H antigens included: (a) multiple antigens distinguishing H-2-matched, inbred strains, and (b) single H antigens, including H-4, H-3, and the male-specific (H-Y) antigen. The involvement of helper T cells in skin allograft rejection and CTL priming was evaluated by pretreating graft recipients with anti-CD4 antibody. Anti-CD4 treatment had no effect on rejection of H-3- and H-4-incompatible skin grafts, but slowed rejection of male and BALB.B skin grafts. Comparable pretreatment with anti-CD4 antibody in vivo eliminated the priming of H-4-specific CTL, multiple B10.BR anti-CBA/J CTL, and all but a minor C57BL/6 anti-BALB.B CTL population. However, CTL specific for the two classes of H antigens, single and multiple minor H antigens, differed in their in vitro requirements for CD4+ helper T cells: (a) multiple antigen-specific CTL required CD4+ helper T cells for optimal expansion, and (b) CTL specific for single H antigens expanded in the absence of helper T cells. The CTL specific for all tested H antigens were CD8+ T cells. These results suggest that CD4+ helper T cells are not always required for effective skin allograft rejection or CTL expansion in vitro; the requirement for helper T cells is apparently dependent upon the identity of the stimulatory minor H antigen(s). This variable dependency contrasts with the evident requirement for helper T cells in the in vivo priming of CTL specific for minor H antigens.
Department of Surgery, Mayo Clinic, Rochester, Minnesota 55905.
P J
PJ
Wettstein
R
R
Korngold
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000032:analysis; D003602:Cytotoxicity, Immunologic; D006084:Graft Rejection; D007111:Immunity, Cellular; D008212:Lymphocyte Depletion; D051379:Mice; D015778:Minor Histocompatibility Antigens / Q000276:immunology*; D016038:Skin Transplantation / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D016827:CD8 Antigens; D015778:Minor Histocompatibility Antigens