Low percentages of circulating CD8(+)/CD45RA(+) human T lymphocytes expressing beta7 integrin correlate with the occurrence of intestinal acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

Objective. Effector phase of acute graft-versus-host disease (a-GVHD) is mainly mediated by donor-derived, anti-host cytotoxic T cells. T-cell homing into gut-associated lymphoid tissues is ascribed to the alpha 4 beta 7 integrin. We reasoned that development of intestinal a-GVHD might be triggered by recruitment in the intestinal mucosa of circulating, alloreactive, alpha 4 beta 7(+) donor T cells. Therefore, we evaluated the correlation existing between circulating beta 7(+) T-lymphocyte subsets early after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and occurrence of a-GVHD.Patients and Methods. Surface expression of 07 integrin on T cells was evaluated by means of direct immunofluorescence, in three-color analysis. Sixty-five patients given allo-HSCT were evaluated: 13 of them experienced intestinal a-GVHD, 14 developed a-GVHD without intestinal involvement, and 38 did not develop a-GVHD. Patients were studied early after initial signs of hematologic reconstitution and before occurrence of a-GVHD.Results. We found a significantly higher absolute number of CD8(+) and a significantly lower percentage of CD8(+)CD45RA(+)beta 7(+) T cells in patients with intestinal a-GVHD than in patients with a-GVHD without intestinal involvement (p = 0.003 and p = 0.003, respectively) or not experiencing a-GVHD (p = 0.02 and p = 0.002, respectively). In particular, we found that intestinal a-GVHD occurred in over 70% of patients showing an absolute number of CD8(+) T cells >= 60 x 10(6)/L and a percentage of circulating CD8(+)CD45RA(+)beta 7(+) T cells < 35%.Conclusion. Measuring the absolute number of CD8(+)T cells and percentage of CD8(+)CD45RA(+)beta 7(+) T cells at time of hematologic reconstitution may help identify patients at risk of developing intestinal a-GVHD who could benefit from strategies aimed at hampering alloreactive T-cell homing to intestinal mucosa. (c) 2006 International Society for Experimental Hematology. Published by Elsevier Inc.