Improvement of decreased interleukin 2 (IL-2) responsiveness and IL-2 production in autologous mixed-lymphocyte reaction of cord blood lymphocytes by interferon-gamma and IL-2 and the role of HLA-DQ antigen.
Cord blood T cells did not produce interleukin 2 (IL-2) nor acquire responsiveness to it in autologous mixed-lymphocyte reaction (AMLR) as they do when activated by phytohemagglutinin (PHA). The ability of the cells to respond to IL-2 was restored either by the addition of recombinant IL-2 to the AMLR culture or by the preculture of non-T stimulator cells with recombinant interferon-gamma (IFN-gamma). IL-2 production was also induced when the T cells were added with recombinant IL-2 at the initiation of the AMLR culture, preceded by the treatment of non-T cells with recombinant IFN-gamma. IL-2-producing cells of cord blood induced in the above-mentioned condition were defined to be OKT4+ T cells, because the deletion of OKT4+ T cells from T-cell population abrogated the reaction, while that of OKT8+ T cells did not. Acquisition of IL-2 responsiveness and IL-2 production of T cells seemed to be mediated by HLA-DR and HLA-DQ molecules of non-T cells because these reactions were blocked by the treatment of non-T cells either with monoclonal anti-HLA-DR or with anti-HLA-DQ antibody. The HLA-DR and HLA-DQ densities of cord blood non-T cells were low as compared with those of adult, but the expression of HLA-DQ was remarkably improved by IFN-gamma treatment. In regard to IL-2, both IFN-gamma and IL-2 were needed to enable the lymphocytes to produce. This may suggest that some functional maturation by IL-2 of responder T cells is further required. These combined data suggested that cord blood non-T cells are defective as a stimulator in AMLR and this could be corrected by enhancing the expression of HLA-DQ antigen.
D005312:Fetal Blood / Q000166:cytology; D006681:HLA-D Antigens / Q000276:immunology*; D006683:HLA-DQ Antigens / Q000276:immunology*; D006801:Humans; D007231:Infant, Newborn / Q000276:immunology*; D007371:Interferon-gamma / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D007959:Lymphocyte Culture Test, Mixed; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D006681:HLA-D Antigens; D006683:HLA-DQ Antigens; D007376:Interleukin-2; D011994:Recombinant Proteins; D007371:Interferon-gamma