Format

Send to:

Choose Destination
See comment in PubMed Commons below
Eur J Immunol. 2011 Sep;41(9):2782-92. doi: 10.1002/eji.201141678. Epub 2011 Aug 18.

Enhancing alloreactivity does not restore GVHD induction but augments skin graft rejection by CD4⁺ effector memory T cells.

Author information

  • 1Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520-8035, USA.

Abstract

Graft-versus-host disease (GVHD) caused by donor T cells attacking recipient tissues is a major cause of morbidity and mortality following allogeneic hematopoietic stem cell transplantation (alloSCT). Studies have shown that effector memory T (T(EM) ) cells do not cause GVHD but are capable of immune functions post-transplant, including graft-versus-leukemia (GVL) effects, but the reasons for this are unclear. In mice, the T(EM) pool may have a less diverse T-cell receptor (TCR) repertoire than naive T (T(N) ) cells with fewer alloreactive clones. We therefore tested whether enhancing the alloreactivity of T(EM) cells would restore their ability to cause GVHD. In an MHC-matched system, alloreactive T(EM) cells were created by transferring GVHD effector cells into syngeneic recipients and allowing conversion to T(EM) cells. Upon retransfer to freshly transplanted recipients, these cells caused only mild GVHD. Similarly, in an MHC-mismatched system, T(EM) cells with a proven increased precursor frequency of alloreactive clones only caused limited GVHD. Nonetheless, these same cells mounted strong in vitro alloresponses and caused rapid skin graft rejection. T(EM) cells created from CD4(+) T cells that had undergone lymphopenia-induced proliferation (LIP) also caused only mild GVHD. Our findings establish that conversion to T(EM) cells significantly reduces GVHD potency, even in cells with a substantially enhanced alloreactive repertoire.

Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Comment in

PMID:
21660940
[PubMed - indexed for MEDLINE]
PMCID:
PMC3517133
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for John Wiley & Sons, Inc. Icon for PubMed Central
    Loading ...
    Write to the Help Desk