Antigen-Specific Priming is Dispensable in Depletion of Apoptosis-Sensitive T Cells for GvHD Prophylaxis.

Shai Yarkoni,Nadir Askenasy,Isaac Yaniv,Jerry Stein

doi:10.3389/fimmu.2014.00215

Shai Yarkoni, Nadir Askenasy + Show 2 more

Open Access

https://doi.org/10.3389/fimmu.2014.00215

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Abstract

Prophylactic approaches to graft versus host disease (GvHD) have employed both phenotypic reduction of T cells and selective elimination of host-primed donor T cells in vitro and in vivo. An additional approach to GvHD prophylaxis by functional depletion of apoptosis-sensitive donor T cells without host-specific sensitization ex vivo showed remarkable reduction in GHD incidence and severity. We address the role and significance of antigen-specific sensitization of donor T cells and discuss the mechanisms of functional T cell purging by apoptosis for GvHD prevention. Host-specific sensitization is dispensable because migration is antigen-independent and donor T cell sensitization is mediated by multiple and redundant mechanisms of presentation of major and minor histocompatibility complex and tissue antigens by donor and host antigen-presenting cells. Our data suggest that potential murine and human GvH effectors reside within subsets of preactivated T cells susceptible to negative regulation by apoptosis prior to encounter of and sensitization to specific antigens.

Highlights

Donor T cells play a dual role in transplantation of hematopoietic stem and progenitor cells (HSPC)
One of the difficulties of fractional phenotypic depletion is the poor correlation between the number of donor T cells and severity of the GvH reaction due to indiscriminate selection of mediators of inflammation [11], as exemplified by vigorous graft versus host disease (GvHD) elicited by antigen-inexperienced T cells in umbilical cord blood (UCB) [12]
GvH simulation by donor T cell sensitization to the host is intuitive, it has been long recognized that cytotoxic T cell assays in vitro correlate poorly with GvH reactivity against minor antigens in vivo [27], possibly because gradual transition to apoptosis-insensitive effector/memory phenotypes in culture may cause persistent recollection of alloresponses in residual T cells

Summary

Introduction

Donor T cells play a dual role in transplantation of hematopoietic stem and progenitor cells (HSPC). One of the difficulties of fractional phenotypic depletion is the poor correlation between the number of donor T cells and severity of the GvH reaction due to indiscriminate selection of mediators of inflammation [11], as exemplified by vigorous GvHD elicited by antigen-inexperienced T cells in umbilical cord blood (UCB) [12].

Results

Conclusion