INDIRECT RECOGNITION OF PORCINE XENOANTIGENS BY HUMAN CD4(-CELL CLONES() T)

Background. Human T-cell response against xenogeneic antigens may occu r either by direct recognition of antigens on xenogeneic antigen-prese nting cells (APCs) or by an indirect pathway mediated by autologous AP Cs. Methods. The proliferative response of human CD4(+) T cells to por cine aortic endothelial cells (PAECs) was measured. From these T-cell lines, eight CD4(+) T-cell clones were obtained by limiting dilution. Results. CD4(+) T cells, in the absence of monocytes, proliferated in response to PAECs only after swine leukocyte antigen (SLA) class II mo lecules were induced on PAECs. The proliferation was significantly bet ter when autologous human monocytes were added back as APCs. All of th e eight CD4(+) T-cell clones demonstrated specific proliferative respo nse when stimulator PAECs, but not PAECs of other porcine origins, wer e preincubated with autologous human APCs before addition of these clo nes. These results indicated that the clones are recognizing porcine x enoantigens presented by self-APCs. The proliferative response of CD4( +) T cell clones was blocked by antibodies directed against human leuk ocyte antigen class II and human CD4, but not by anti-SLA class II mon oclonal antibodies. A marked inhibition in proliferation was also note d when human APCs were incubated with chloroquine before addition to t he cultures, indicating that xenoantigens had to be processed in order to be recognized by the clones. Conclusions. Human CD4(+) T cells can recognize xenoantigens by either a direct or indirect pathway. The CD 4(+) T-cell clones developed against SLA class II-negative PAECs recog nized strain-specific porcine xenoantigens indirectly.