Inability of activated cord blood T lymphocytes to perform Th1-like and Th2-like responses: Implications for transplantation

Cytokines secreted by alloreactive donor T cells play a crucial role in the pathogenesis of both acute and chronic GvHD, a complication of allogeneic hematopoietic transplants that occurs at a lower incidence and severity when human umbilical cord blood (HUCB) is used, Our five-dimensional flow cytometric study performed on 20 HUCB and 20 peripheral blood (PB) samples from healthy adults was focused on the Th1/Th2 cytokine profile of activated HUCB T cells, Lymphocytes of all samples were stimulated by specific mitogens, and cytokine secretion was blocked at the cytoplasmic level. CD4(+) and CD8(+) cells were then analyzed for surface expression of the very early human activation antigen CD69 and for IFN-gamma and IL-4 intracellular production as expression of Th1-like and Th2-like T cell cytokine response, respectively, HUCB T lymphocytes were shown to be unable to perform both a Th1-like and Th2-like response, as compared with normal PB T cells, However, all lymphocytes from both sources were normally activated, as indicated by regular expression of the CD69 molecule. These data suggest that the low response of HUCB T lymphocytes to mitogens may be responsible for the decreased incidence of acute and chronic GvHD and provide possible explanations for the clinical results in HUCB transplantation.