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Recipient CD4+ T cells that survive irradiation regulate chronic graft-versus-host disease.

Abstract：

:Chronic graft-versus-host disease (cGVHD) is an increasingly common cause of morbidity and mortality in allogeneic stem cell transplantation (alloSCT). Relative to acute GVHD (aGVHD), much less is understood about cGVHD. Using the B10.D2 --> BALB/c murine cGVHD model, which shares critical pathologic features with human cGVHD, we find that radiation-resistant host T cells regulate cGVHD. We initially observed that recipients lacking all lymphocytes developed accelerated and more severe cGVHD. Using genetically deficient recipients, we determined that alphabeta+CD4+ T cells were required to regulate cGVHD. Increased cGVHD severity was not due to the absence of T cells per se. Rather, the potency of regulation was proportional to host T-cell receptor (TCR) diversity. Only CD4+CD25+, and not CD4+CD25-, host T cells ameliorated cGVHD when added back, indicating that host T cells acted not via host-versus-graft activity or by reducing homeostatic proliferation but by an undefined regulatory mechanism. Thus, preparative regimens that spare host CD4+CD25+ T cells may reduce cGVHD. Donor CD4+CD25+ T cells also reduced cGVHD. Depletion of CD4+CD25+ cells from the inoculum exacerbated disease, whereas transplantation of additional CD4+CD25+ cells protected against severe cGVHD. Additional CD4+CD25+ cells also promoted healing of established lesions, suggesting that their effects persist during the evolution of cGVHD.

journal_name

Blood

journal_title

Blood

authors

Anderson BE,McNiff JM,Matte C,Athanasiadis I,Shlomchik WD,Shlomchik MJ

doi

10.1182/blood-2004-01-0328

subject

Has Abstract

pub_date

2004-09-01 00:00:00

pages

1565-73

issue

5

eissn

0006-4971

issn

1528-0020

pii

2004-01-0328

journal_volume

104

pub_type

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