Cytokine activity after allogeneic bone marrow transplantation. V. Analysis of IL-2 and IFN production by isolated CD4+ and CD8+ cells

Previous studies from this laboratory have shown that PBMC from recipients of an HLA-identical sibling bone marrow transplant produce levels of IL-2 which are 10-100-fold lower than those produced by the same number of PBMC from healthy controls, whereas production of IFN-gamma is normal. The present study examined IL-2 and IFN production over a range of cell numbers for PBMC and for isolated CD4+ and CD8+ cells for controls and marrow transplant recipients. There was a 5-fold lower IL-2 production in marrow transplant recipient CD8+ cells compared with equivalent numbers of control cells, whereas no difference was found in IL-2 production by CD4+ cells. In contrast, IFN production by CD4+ cells from marrow transplant recipients was 4-fold higher than in controls, whereas CD8+ cells from both populations produced similar amounts of IFN. When the observed production of cytokine by PBMC was compared with the expected production based on the CD4+ and CD8+ content of the PBMC, control values were similar, but the expected values for both cytokines were approximately 2-fold higher than the observed values for marrow transplant recipients. The results suggest that the capacity of T cells from marrow transplant recipients to produce IL-2 and IFN is not impaired, but that the frequency of cytokine-producing cells may be reduced, and that a negative interaction present in recipient PBMC, eliminated by isolating T-cell subsets, is responsible for the observed low levels of cytokine production.