CD4-positive/heat-stable antigen-positive thymocytes cause graft-versus-host disease across non-major histocompatibility complex incompatibilities.
Single-positive thymocytes are the immediate precursors of peripheral recent thymic emigrants (RTE) which develop into mature peripheral T cells. The functional ability of RTE is unclear but their state of differentiation may be relevant to the development of tolerance to peripheral "self" antigens. Since RTE are difficult to analyze, precursor CD4+/8- thymocytes were assessed in a model in vivo to determine their functional capability and their susceptibility to tolerance induction. The ability of both heat-stable antigen-positive (HSA+) (immature) and HSA- (mature) single-positive thymocytes to cause graft-versus-host disease (GVHD) across non-major histocompatibility complex differences were examined. Both HSA- and HSA+ CD4+/8- thymocytes from C3H mice caused lethal GVHD in AKR recipients as did CD4+ peripheral T cells in controls. Further, neonatal C3H thymocytes also caused lethal GVHD in AKR recipients. Since CD4+/8- thymocytes are the precursors of RTE, these results suggest that RTE are not susceptible to tolerance induced to "minor" antigens and may have a normal immune function in vivo. This would suggest that peripheral tolerance may be dependent upon the manner of antigen presentation rather than T cell maturity.
Charlton
B
B
Department of Medicine, Stanford University Medical School, CA 94305.
Meltzer
J
J
Fathman
C G
CG
D000818:Animals; D000831:Animals, Newborn / Q000276:immunology; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology*; D051927:CD24 Antigen; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology; D008285:Major Histocompatibility Complex / Q000235:genetics*; D008562:Membrane Glycoproteins; D051379:Mice; D008806:Mice, Inbred AKR; D008809:Mice, Inbred C3H; D013950:Thymus Gland / Q000166:cytology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D051927:CD24 Antigen; C497890:Cd24a protein, mouse; D008562:Membrane Glycoproteins