CD103 blockade reduces CD8 T cell accumulation during GVHD, but does not attenuate GVL effects. (169.35)
Year: 2011
Type: conference-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.
Source: The Journal of Immunology
Institution: The Ohio State University
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W1591560789