Direct activation of human responder T cells by porcine stimulator cells leads to T cell proliferation and cytotoxic T cell development

Abstract: Functional activities of highly purified T human responder lymphocytes reactive against porcine stimulator cells were studied to evaluate whether porcine stimulator cells can directly activate a xenospecific cellular immune response. Mixed lymphocyte culture (MLC) tests revealed that CD4+ human responder cells proliferate when stimulated in vitro with porcine cells, a reaction similar to that of alloresponses regarding magnitude and tempo. A direct pathway of activation was verified by the requirement for adherent porcine stimulator cells and the partial blocking by monoclonal antibodies against porcine major histocompatibility complex (MHC) class II antigens. An analysis of proliferative CD4+, CD3+, CD16-, and 56- human T cell clones revealed that some clones were seemingly recognizing allele-specific determinants, whereas others could be restimulated by a wide range of porcine stimulator cells. Cytotoxic T cells (CTLs) were generated following direct recognition of pig cell ligands by human T cells in the absence of autologous antigen-presenting cells (APCs). Although the identification of target antigen(s) on the pig cell recognized by the CTL warrants some discussion, the pattern of killing exhibited by the CTLs indicates the recognition of porcine polymorphic determinant(s). The implications of these findings for cellular reactivity against porcine transplants are discussed.