High frequencies of CD62L+ naive regulatory T cells in allografts are associated with a low risk of acute graft-versus-host disease following unmanipulated allogeneic haematopoietic stem cell transplantation

Abstract

Regulatory T cells (T(regs) ) play a key role in the prevention of acute graft-versus-host disease (aGVHD). To investigate the association between T(reg) subsets and aGVHD, we prospectively analysed T cell subsets in the allografts of 35 patients undergoing myeloablative unmanipulated haematopoietic stem cell transplantation. Multivariate analysis found that patients infused with less than 0·29 × 10(6) /kg of CD4(+) CD25(high) CD45RA(+) CD62L(+) T cells during transplantation exhibited an increased incidence of II-IV aGVHD [hazard ratio (HR) = 0·000, 95% CI = 0·000-0·106, P = 0·013]. Next, we compared the reconstitution characteristics of T cell subsets between haploidentical haematopoietic stem cell transplantation (HSCT) and sibling HSCT by collecting peripheral blood samples at regular intervals (days 30, 60 and 90) after transplantation. No significant differences were observed in the reconstitution of conventional T cells between haploidentical HSCT and sibling identical HSCT. However, total counts of recovered naiveT(regs) and CD62L(+) naive T(regs) from haploidentical HSCT were significantly lower compared to sibling identical HSCT; P-values were 0·045 and 0·021, respectively. Although total counts of conventional T cells in aGVHD patients reached similar levels compared to non-aGVHD patients before day 60 post-HSCT, total counts of naive T(regs) and CD62L(+) naive T(regs) in aGVHD patients did not reach similar levels to non-aGVHD patients until 90 days post-HSCT. Taken together, our findings demonstrate that a large population of CD62L(+) naive T(regs) in allografts reduces the incidence of aGVHD. Further, development of aGVHD is related closely to the delayed reconstitution of the naive T(reg) population.