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 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.
D000328:Adult; D000818:Animals; D018122:B7-1 Antigen / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018968:CD58 Antigens / Q000502:physiology*; D002461:Cell Line, Transformed; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D008213:Lymphocyte Activation; D051379:Mice; D051381:Rats
D018122:B7-1 Antigen; D018968:CD58 Antigens; D006684:HLA-DR Antigens; D018799:Intercellular Adhesion Molecule-1