Development of graft-vs.-host disease-like syndrome in cyclosporine-treated rats after syngeneic bone marrow transplantation. I. Development of cytotoxic T lymphocytes with apparent polyclonal anti-Ia specificity, including autoreactivity.
Lethally irradiated rats reconstituted with syngeneic bone marrow and treated with cyclosporine (CsA) for 40 d develop a graft-vs.-host disease-like syndrome (GVHD) after CsA therapy. We attempted to assess the development of autoreactivity in these animals. Results revealed that a majority of the animals with syngeneic GVHD develop autocytotoxic T lymphocytes of the OX8 phenotype. In addition to reactivity with self, these cells were capable of lysing appropriate target cells from a variety of different rat strains. The target antigens appeared to be class II major histocompatibility antigens, because lysis could be effectively blocked by an anti-Ia monoclonal antibody. Cold target inhibition studies indicated that one effector cell was capable of lysing various target cells, and provided evidence against a polyclonal activation of multiple anti-Ia-reactive cells. These results suggested that the anti-class II autoreactive cell associated with syngeneic GVHD either recognizes a common class II determinant ("public" epitope) shared by multiple strains of rats, or was polyspecific with respect to "private" class II determinants.
Hess
A D
AD
Horwitz
L
L
Beschorner
W E
WE
Santos
G W
GW
D000818:Animals; D016026:Bone Marrow Transplantation; D002999:Clone Cells / Q000276:immunology; D003524:Cyclosporins / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D000939:Epitopes; D005260:Female; D006086:Graft vs Host Disease / Q000139:chemically induced / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D051381:Rats; D011912:Rats, Inbred ACI; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D013154:Spleen / Q000166:cytology; D013577:Syndrome; D013602:T-Lymphocytes, Cytotoxic / Q000145:classification* / Q000276:immunology; D014185:Transplantation, Isogeneic
D003524:Cyclosporins; D000939:Epitopes; D000949:Histocompatibility Antigens Class II