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The intensity and mechanisms of cell-mediated rejection of pig islet cells were studied in 49 Type I diabetic and 34 healthy subjects. Human peripheral mononuclear cells proliferated strongly in response to pig islet cells (p&lt;0.001), though with notable interindividual variations (stimulation index 2 to 215). The variance of stimulation index was higher in diabetic than healthy subjects (p&lt;0.0001). The response to islet cells was stronger (p&lt;0.01) than that to pig splenocytes. Proliferation in response to islet cells was strongly decreased (p&lt;0.01) when CD4+ T cells were blocked with monoclonal antibodies, whereas the blocking of CD8+ cells or NK cells gave less pronounced effects. The response to islet cells was decreased (p&lt;0.01), but not abolished, after antigen-presenting cells were removed. Purified CD4+ cells alone did not proliferate in response to islet cells but recovered their proliferative ability when mixed with antigen-presenting cells, whereas CD8+ cells alone proliferated in the presence of interleukin-2 in response to islet cells. Proliferation was blocked (p&lt;0.01) by anti-DR monoclonal antibodies. During proliferation in response to islet cells, interleukin-10 increased 43-fold (p&lt;0.01) but interferon-gamma increased only slightly. No statistical differences were detected between diabetic and control subjects with respect to lymphocyte subsets and the recognition mechanisms or to interferon-gamma/interleukin-10 production in response to islet cells. These results provide the first detailed information on human cell-mediated xenoreaction to pig islet cells. This situation involves a dominant CD4 class II-restricted Th2 response, with an indirect recognition pathway, as well as a CD8 T-cell response resulting from direct recognition. This strong reaction constitutes a serious obstacle which may vary in degree among subjects.

diabetologia

Intensity and mechanisms of in vitro xenorecognition of adult pig pancreatic islet cells by CD 4 + and CD 8 + lymphocytes from Type I diabetic or healthy subjects