Erythropoietin exerts direct immunomodulatory effects on the cytokine production by activated human T-lymphocytes.

The effect of erythropoietin-β (Epo-β) on the functional profile of activated human T-lymphocytes remains largely unknown, which hinders clinical application of Epo as an immunomodulatory agent. We studied the direct impact of Epo on the activation status of human T lymphocytes following activation by particles loaded with antibodies (Abs) against human CD2, CD3, and CD28. T cell activation was assessed by the surface expression of CD38 activation marker. Epo did not significantly affect activation status of both CD4(+) and CD4(-) T cells, as well as of naive (CD45RA(+)CD197(+)), central memory (CD45RA(-)CD197(+)), effector memory (CD45RA(-)CD197(-)), and terminally-differentiated (CD45RA(+)CD197(-)) T cells. However, Epo markedly augmented production of IL-2, IL-4 and IL10 by activated T cells with concomitant reduction in IFN-γ secretion. Taken together, our data showed that Epo could directly down-regulate pro-inflammatory T cell responses without affecting T cell activation status.