Characterization of OX40+ T cells detected in patients with GVHD after hematopoietic stem cell transplantation

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We studied the role of the OX40/OX40L in GVHD that is though to be ascribed to alloreactive immune response of donor-derive T cells to recipient cells.We examined the expression of OX40 on peripheral blood T cells of post-stem cell transplantation patients after day 100. The percentages of both OX40^+CD4^+ and OX40^+CD8^+ T cells were significantly higher in patients with chronic c GVHD than those without. Serial analyses showed that OX40^+CD4^+ T cells elevated before the onset of cGVHD and at the onset closely correlated with the therapeutic response. These results indicated that serial measurement of OX40^+ T cells is useful for predicting the onset as well as therapeutic response of cGVHD and raised a possibility that the OX40/gp34 system is involved in the pathogenesis of cGVHD (Blood 98:3162, 2001). To define the role of the OX40/OX40L system in alloreactivity in more detail, we examined the effect of anti-OX40L mAb on proliferative response of CD4^+ T cells to allogeneic monocyte-derived DCs. We observed that expression of OX40 was dependent on CD28 signals and anti-OX40L mAb markedly inhibited proliferative response of CD4^+ T cells to allogeneic DC and even to sorted OX40L^- DC, indicating that the OX40/OX40L system plays a crucial role in allogeneic T cell immune response (Immunology, 109:226-231, 2003). We found that OX40 signaling induces production of RANTES at both mRNA and protein levels by vascular endothelial cells, which we first identified in screening with cDNA array (Immunol. Lett. 84:1, 2002). Now that CCR5^+ T cells are considered to initiate GVHD (Nature Immunol. 4:154, 2003), this finding may be of pathophysiological relevance.