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

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.

journal_name

Eur J Immunol

journal_title

European journal of immunology

authors

Anderson BE,Tang AL,Wang Y,Froicu M,Rothstein D,McNiff JM,Jain D,Demetris AJ,Farber DL,Shlomchik WD,Shlomchik MJ

doi

10.1002/eji.201141678

subject

Has Abstract

pub_date

2011-09-01 00:00:00

pages

2782-92

issue

9

eissn

0014-2980

issn

1521-4141

journal_volume

41

pub_type

杂志文章

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