Background: Human T-cell response against xenogeneic antigens may occur either by direct recognition of antigens on xenogeneic antigen-presenting cells (APCs) or by an indirect pathway mediated by autologous APCs.
Methods: The proliferative response of human CD4+ T cells to porcine 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 molecules were induced on PAECs. The proliferation was significantly better when autologous human monocytes were added back as APCs. All of the eight CD4+ T-cell clones demonstrated specific proliferative response when stimulator PAECs, but not PAECs of other porcine origins, were preincubated with autologous human APCs before addition of these clones. These results indicated that the clones are recognizing porcine xenoantigens presented by self-APCs. The proliferative response of CD4+ T-cell clones was blocked by antibodies directed against human leukocyte antigen class II and human CD4, but not by anti-SLA class II monoclonal antibodies. A marked inhibition in proliferation was also noted when human APCs were incubated with chloroquine before addition to the 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 CD4+ T-cell clones developed against SLA class II-negative PAECs recognized strain-specific porcine xenoantigens indirectly.