CD103 blockade reduces CD8 T cell accumulation during GVHD, but does not attenuate GVL effects. (169.35)

Abstract

Abstract Graft versus host disease (GVHD) remains the salient barrier to broader use of hematopoietic stem cell transplantation (SCT) as a curative therapy for hematological malignancy. Although multiple means exist to neutralize donor-reactive T cells, such strategies have the potential to inhibit graft-vs-leukemia (GVL) effects, leaving the host vulnerable to relapse. The goals of the present study were: 1) to define the role of CD103 in promoting accumulation of donor CD8 T cells in the host gut following SCT, 2) assess the role of CD103 in promoting GVL effects. Following CD4 depletion, donor specific CD8 T cells selectively accumulated in the host gut epithelium in either MHC-matched or MHC-mismatched SCT models. Moreover, CD103 expression by CD8 T cells increased dramatically over time in both models. BLI studies revealed that CD103 expression is required for efficient accumulation of donor CD8 T cells in the host gut. BLI studies using TCR transgenic CD8 T cells co-expressing luciferase revealed that host-specific CD8 T cells preferentially accumulate in the host gut (as compared to the host spleen) during GVHD. Using a model of human chronic lymphocytic leukemia (CLL), we found that CD103 was not required for effective clearance of malignant B cells. These data indicate CD103 deficiency selectively attenuates GVHD pathology without compromising GVT effects, identifying CD103 as a potential target for GVHD prophylaxis.