The role of major histocompatibility complex and non-major 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 alloantigen differences in generating nonsuppurative cholangitis during graft-vs.-host disease. Transfer of C57BL/6J (B6) splenocytes to class I major histocompatibility complex-disparate bm1 x B6 F1, class II major histocompatibility complex-disparate B6 x bm12 F1, or multiple non-major histocompatibility complex antigen-disparate Balb,B x B6 F1 mice led to the development of periportal inflammatory infiltrates and lymphocyte invasion of bile duct walls. However, frank destruction of bile duct walls was observed only in strain combinations with class I major histocompatibility complex or multiple non-major histocompatibility complex-encoded disparities. The concomitant presence of class II major histocompatibility complex differences and class I major histocompatibility complex or multiple non-major histocompatibility complex differences did not increase and in some cases was associated with less severe bile duct disease than was observed in strain combinations with discrete histocompatibility antigen differences. Depletion of L-leucyl-L-leucine methyl ester-sensitive cytotoxic T lymphocytes from donor inocula reduced the incidence of destructive bile duct lesions observed early 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-leucine methyl ester-resistant T helper cells alone was sufficient to generate destructive cholangitis in class I+II major histocompatibility complex-disparate or multiple non-major histocompatibility complex antigen-disparate strain combinations.(ABSTRACT TRUNCATED AT 250 WORDS)