Intensity and mechanisms of in vitro xenorecognition of adult pig pancreatic islet cells by CD4+ and CD8+ lymphocytes from type I diabetic or healthy subjects.
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<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<0.0001). The response to islet cells was stronger (p<0.01) than that to pig splenocytes. Proliferation in response to islet cells was strongly decreased (p<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<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<0.01) by anti-DR monoclonal antibodies. During proliferation in response to islet cells, interleukin-10 increased 43-fold (p<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.
Lalain
S
S
Cellular and Molecular Immuno-Endocrinology, University/INRA/ENVN, Nantes, France.
Chaillous
L
L
Gouin
E
E
Saï
P
P
D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D012016:Reference Values; D013154:Spleen / Q000276:immunology; D013552:Swine; D014183:Transplantation, Heterologous / Q000276:immunology
D000911:Antibodies, Monoclonal