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

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Abstract
Conflicting data have been reported regarding the relative abilities of B7, ICAM-1 and LFA-3 to provide co-stlmulatlon for the Induction of a primary T cell alloprollferative response. A series of naturally HLA-DR-expressing cell lines and panels of human and murlne transfectants expressing DR alloantlgens 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 alloproliferatlve 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 allostlmulation observed in response to DR-expressing murine DAP.3 cells, that constltutively express B7.1, was Inhibited by the presence of the murlne cytolytic T lymphocyte-associated antigen 4-human Fcγ1 fusion protein, suggesting that mouse B7.1 provides sufficient costimulation for a primary human alloproliferatlve response. Expression of supranormal levels of human B7.1 on the allostimulator cells led to a reduction In the proliferatlve 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 proliferatlve 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 immunogenlclty with relevance to Inhibiting unwanted immune responses to transplanted tissues and provoking anti-tumour immunity.

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