Human T cell responses to human and procine endothelial cells are highly sensitive to cyclosporin A and FK506 in vitro

Background Human T cells proliferate in response to both human umbilical ve in endothelial cells (HUVEC) and porcine aortic endothelial cells (PAEC) vi a the second signals LFA-3/CD2 and B7-2 (CD86), respectively, Previous stud ies have shown that stimulation of T cells via CD28 or phorbol myristate ac etate (PMA) activation is highly resistant to inhibition by cyclosporine A (CsA) and tacrolimus (FK506), as is the response of T cells to phytohemmagl utinin in the presence of endothelial cells. We have investigated the inhib itory effects of CsA and FK506 on the direct response of human CD4(+) T cel ls to HUVEC and PAEC and the effect of adding B7-1 transfectants. Methods. T cell proliferation, interleukin-2 release bioassays and a multip le cytokine bioassay employing the TF-1 cell line were used as indicators o f T cell responses to HUVEC and PAEC either in the presence or absence of C sA and FK506. In some experiments, B7-1 transfectants were also added, Results, Proliferative responses and interleukin-2 release were highly sens itive to CsA, the ID50 being significantly less for HUVEC(6.5 ng/ml) than P AEC (15 ng/ml). The ID50 of CsA for the mixed lymphocyte response (MLR) was similar to PAEC (18.6 ng/ml), all these values being significantly less th an the T cell activation by phytohemmaglutinin (PHA) (227 ng/ml), Addition of B7-1 transfectants significantly increased interleukin-a production by T cells/HUVEC and resistance to CsA was greatly increased to an I-50, of > 1 000 ng/ml, In contrast, addition of B7-1 transfectants to T cells/PAEC had no effect either on T cell proliferation, IL-2 production, or CsA resistanc e. Similar results were obtained with FK506. Using the TF-1 cell line, it w as determined that cytokines other than IL-2 are released during CD4(+) T c ell/EC interactions, with similar sensitivity to CsA and FK506, Conclusions. It is concluded that both allogeneic and xenogeneic T cell/end othelial responses should be inhibited by therapeutic levels of CsA in vivo , assuming the absence of trans-stimulation by B7 molecules.