Host resistance to cyclosporine induced syngeneic graft-versus-host disease. Requirement for two distinct lymphocyte subsets.
Cyclosporine is crucial for the prevention of organ allograft rejection and allogeneic graft-vs-host disease (GVHD). Despite its potent immunosuppressive activity, cyclosporine elicits a T cell-mediated autoimmune syndrome after autologous or syngeneic bone marrow transplantation, which has been termed syngeneic GVHD (SGVHD). Recent studies have shown that for disease manifestation, a cytoxan and radiation-sensitive T cell dependent host resistance mechanism must be eliminated, allowing the clonal expansion of autoreactive cells. This report characterizes the autoregulatory lymphocyte population, present in normal animals, capable of inhibiting the adoptive transfer of SGVHD. First, twice the number of unfractionated splenocytes from normal animals to those from autoimmune donors ensured complete inhibition of the adoptive transfer of immune reactivity. Second, the phenotype of this host resistance mechanism in normal splenocytes involves dual regulatory T cell subsets. A helper/inducer subset (W3/25+) must be cotransferred with a cytotoxic/suppressor subset (OX8+) in a ratio that approximates the normal ratio in normal unfractionated splenocytes in order to affect inhibition of the transfer of SGVHD. Moreover the specific inducer regulatory activity resides in the OX22-, W3/25+ subset of Th cells.
Fischer
A C
AC
Oncology Center, Johns Hopkins University, Baltimore, MD 21205.
Laulis
M K
MK
Horwitz
L
L
Beschorner
W E
WE
Hess
A
A
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte; D003524:Cyclosporins; D005260:Female; D006086:Graft vs Host Disease / Q000139:chemically induced / Q000276:immunology*; D007108:Immune Tolerance / Q000187:drug effects; D007113:Immunity, Innate / Q000187:drug effects; D007116:Immunization, Passive; D010641:Phenotype; D051381:Rats; D011917:Rats, Inbred Lew; D013154:Spleen / Q000637:transplantation; D013601:T-Lymphocytes / Q000145:classification* / Q000276:immunology / Q000637:transplantation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000637:transplantation; D006377:T-Lymphocytes, Helper-Inducer / Q000145:classification / Q000276:immunology / Q000637:transplantation
D000945:Antigens, Differentiation, T-Lymphocyte; D003524:Cyclosporins