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Cytokine modulation of HLA-DR expression on proliferating cord blood T cells
HLA class II antigens are not expressed on resting T cells, but upon activation, their expression is readily induced on most mature T cells. T cells derived from cord blood (CB), however, remain HLA class II even when actively proliferating. To examine the reason for this deficiency, we have now tried to modulate HLA class II expression with three cytokines: interferon-gamma (IFN-gamma), tumor necrosis factor (TNF), and interleukin-1 (IL-1); all of which are known to modulate HLA class II expression in various cell types. Although CB T cells are not, in contrast to mature T cells, able to produce IFN-gamma, IFN-gamma did not have any effect on the amount of cell surface HLA-DR antigens. IL-1 was also without effect, but TNF increased the proportion of HLA-DR+ cells in both CB and adult peripheral blood (PBL)-derived T lymphoblasts. Northern blotting analysis of the HLA-DR mRNA levels revealed that in CB cells the levels were 5-6 times lower than in the PBL-derived lymphoblasts, indicating that the lower HLA-DR antigen expression in CB T cells is due to transcriptional regulation. Of the cytokines tested, only TNF had an effect on the steady-state HLA-DR mRNA levels, increasing the levels in both CB and PBL-derived T-blasts 2-3-fold.
HLA class II antigens are not expressed on resting T cells, but upon activation, their expression is readily induced on most mature T cells. T cells derived from cord blood (CB), however, remain HLA class II even when actively proliferating. To examine the reason for this deficiency, we have now tried to modulate HLA class II expression with three cytokines: interferon-gamma (IFN-gamma), tumor necrosis factor (TNF), and interleukin-1 (IL-1); all of which are known to modulate HLA class II expression in various cell types. Although CB T cells are not, in contrast to mature T cells, able to produce IFN-gamma, IFN-gamma did not have any effect on the amount of cell surface HLA-DR antigens. IL-1 was also without effect, but TNF increased the proportion of HLA-DR+ cells in both CB and adult peripheral blood (PBL)-derived T lymphoblasts. Northern blotting analysis of the HLA-DR mRNA levels revealed that in CB cells the levels were 5-6 times lower than in the PBL-derived lymphoblasts, indicating that the lower HLA-DR antigen expression in CB T cells is due to transcriptional regulation. Of the cytokines tested, only TNF had an effect on the steady-state HLA-DR mRNA levels, increasing the levels in both CB and PBL-derived T-blasts 2-3-fold.