THE PRIMARY ALLORESPONSE OF HUMAN CD4(+) T-CELLS IS DEPENDENT ON B7 (CD80), AUGMENTED BY CD58, BUT RELATIVELY UNINFLUENCED BY CD54 EXPRESSION

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 1 fusion protein, suggesting that mouse 87,1 provides sufficient co-stimulation 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 87 exists which, if exceeded, leads to inhibition. Go-expression of LFA-3 with B7.1 by the allostimulator cells caused a marked increase in the proliferative response, Expression of ICAM-1 had relatively little effect, No differences were seen in the co-stimulatory requirements of naive cord blood versus CD45RO adult T cells, These results highlight the key molecular interactions that govern immunogenicity with relevance to inhibiting unwanted immune responses to transplanted tissues and provoking anti-tumour immunity.