THE ROLE OF MAJOR HISTOCOMPATIBILITY COMPLEX AND NONMAJOR HISTOCOMPATIBILITY COMPLEX ENCODED ANTIGENS IN GENERATION OF BILE-DUCT LESIONS DURING HEPATIC GRAFT-VS-HOST RESPONSES MEDIATED BY HELPER OR CYTOTOXIC T-CELLS

In these studies, we examined the role of discrete classes of alloanti gen differences in generating non-suppurative cholangitis during graft -vs.-host disease. Transfer of C57BL/6J (B6) splenocytes to class I ma jor histocompatibility complex-disparate bm1 x B6 F1, class II major h istocompatibility complex-disparate B6 x bm12 F1, or multiple non-majo r histocompatibility complex antigen-disparate Balb,B x B6 F1 mice led to the development of periportal inflammatory infiltrates and lymphoc yte invasion of bile duct walls. However, frank destruction of bile du ct walls was observed only in strain combinations with class I major h istocompatibility complex or multiple non-major histocompatibility com plex-encoded disparities. The concomitant presence of class II major h istocompatibility complex differences and class I major histocompatibi lity complex or multiple non-major histocompatibility complex differen ces did not increase and in some cases was associated with less severe bile duct disease than was observed in strain combinations with discr ete histocompatibility antigen differences. Depletion of L-leuCyl-L-le ucine methyl ester-sensitive cytotoxic T lymphocytes from donor inocul a reduced the incidence of destructive bile duct lesions observed earl y in the course of graft-vs.-host disease in B6-->Balb.B x B6 F1 or B6 -->bm1 x B6 F1 mice. However, transfer of CD8-negative, L-leucyl-L-leu cine methyl ester-resistant T helper cells alone was sufficient to gen erate destructive cholangitis in class I + II major histocompatibility complex-disparate or multiple non-major histocompatibility complex an tigen-disparate strain combinations. These findings demonstrate that h istologically similar patterns of destructive nonsuppurative cholangit is can be generated by diverse T effector mechanisms directed at class I major histocompatibility complex or non-major histocompatibility co mplex-encoded antigen differences. However, in this murine graft-vs.-h ost disease model, the presence of class II major histocompatibility c omplex-encoded alloantigen differences provided neither a direct nor a n additive stimulus for generation of destructive duct lesions.