THE HOST RESPONSE IN GRAFT-VERSUS-HOST DISEASE .3. THE IN-VITRO INDUCTION OF REGULATORY CELLS IN CHRONIC MURINE GRAFT-VERSUS-HOST DISEASE

Murine graft versus host (GVH) disease takes two forms depending upon the parental/F1 strain combination employed, Acute lethal GVH disease is characterized by anemia, lymphopenia, hypogammaglobulinemia, profound anti-F1 cytotoxicity, and the loss of cytotoxic potential against third-party alloantigen. In contrast to this, chronic GVH disease is characterized by polyclonal B cell activation, autoantibody production, no anti-F1 cytotoxicity, and retained cytotoxicity against allotargets. We have previously reported that this marked disparity in disease expression results from a radiosensitive host cell which protects the F1 mouse from parental anti-F1 CTX in mice undergoing CGVH disease, Using an in vitro system to induce the host protective cell, we now demonstrate that two distinct Thy-1(+) cells emerge which regulate CTX against the host. One cell is of host origin, radiation sensitive, and functionally resembles a veto cell, The second regulatory cell, of parental origin, is radiation resistant and restricted in its ability to suppress anti-F1 CTX: We further demonstrate that the emergence of these cells is modulated by competitive immunoregulatory influences mediated by T contrasuppressor and I-J(+) cells. (C) 1995 Academic Press, Inc.