The primary alloresponse of human CD4+ T cells is dependent on B7 (CD80), augmented by CD58, but relatively uninfluenced by CD54 expression

Abstract

Conflicting data have been reported regarding the relative abilities of B7, ICAM-1 and LFA-3 to provide co-stimulation for the induction of a primary T cell alloproliferative response. A series of naturally HLA-DR-expressing cell lines and panels of human and murine transfectants expressing DR alloantigens in conjunction with combinations of mouse or human B7.1, human LFA-3 and human ICAM-1 were used to analyse the contributions of these molecules to primary alloproliferative responses by adult and cord blood CD4+ T cells. The results demonstrated that B7 expression is required, and may be sufficient for the induction of a primary alloresponse. The allostimulation observed in response to DR-expressing murine DAP.3 cells, that constitutively express B7.1, was inhibited by the presence of the murine cytolytic T lymphocyte-associated antigen 4-human Fc gamma 11 fusion protein, suggesting that mouse B7.1 provides sufficient costimulation for a primary human alloproliferative response. Expression of supranormal levels of human B7.1 on the allostimulator cells led to a reduction in the proliferative response, suggesting that an optimal level of B7 exists which, if exceeded, leads to inhibition. Co-expression of LFA-3 with B7.1 by the allostimulator cells caused a marked increase in the proliferative response. Expression of ICAM-1a had relatively little effect. No differences were seen in the co-stimulatory requirements of naive cord blood versus CD45RO adult T cells. There results highlight the key molecular interactions that govern immunogenicity with relevance to inhibiting unwanted immune response to transplanted tissues and provoking anti-tumour immunity.