Format

Send to

Choose Destination
See comment in PubMed Commons below
J Heart Lung Transplant. 2008 Jun;27(6):616-22. doi: 10.1016/j.healun.2008.02.015.

Role for CD4(+)CD25(+) T cells in inhibition of graft rejection by extracorporeal photopheresis.

Author information

1
Department of Surgery, University of Alabama at Birmingham, AL 35294, USA. jgeorge@uab.edu

Erratum in

  • J Heart Lung Transplant. 2008 Oct;27(10):1190. Guo, Wing Hong [corrected to Guo, Lingling].

Abstract

BACKGROUND:

Extracorporeal photopheresis (ECP) is used to treat recurrent severe rejection in clinical heart and lung recipients. The mechanisms of the salutary effects of ECP are poorly understood, but appear to involve regulation of T-cell-mediated alloreactive responses, possibly by induction of regulatory T cells. We created a mouse model of ECP to determine the effects of ECP on T-cell responses in vivo and the contribution of CD4(+)CD25(+) T cells.

METHODS:

In this study, 1 x 10(7) splenocytes were treated with 8-methoxypsoralen (8-MOP, 200 ng/ml), followed by ultraviolet A (UVA) irradiation (2 J/cm(2), 350 nm), and then injected intravenously into syngeneic mice. Thirty minutes later, the treated animals received heterotopic cardiac allografts with no immunosuppression. Treated graft recipients were analyzed to determine the effect of ECP on graft survival, deletion of allospecific T cells, and the frequency and in vivo suppressive activity of CD4(+)CD25(+) T cells.

RESULTS:

ECP extends cardiac allograft survival in at least two different strain combinations. For CBA/Ca recipients of C57BL/6 allografts, median survival time (MST) in ECP-treated animals was 16 days vs 10 days in graft recipients treated with cells exposed only to 8-MOP (p = 0.04). The frequency of splenic CD4(+)CD25(+) cells expressing FoxP3(+) increased 2-fold in ECP-treated CBA/Ca mice (82.6 +/- 5.2%, n = 4) relative to untreated mice (44.9 +/- 4.5%, n = 4, p < 0.001). Adoptive transfer of 3 x 10(5) sorted CD4(+)CD25(+) splenocytes from ECP-treated graft recipients to untreated cardiac allograft recipients 30 minutes after transplantation resulted in extended graft survival compared with animals that received the same number of CD4(+)CD25(+) splenocytes from cardiac allograft recipients not treated with ECP (MST: 24 days vs 13 days, respectively, p = 0.001). Analyses of 5,6-carboxy-fluorescein-succinimidyl-ester (CFSE)-labeled H-2K(b)-specific T cells in the spleen and lymph node showed no evidence of peripheral deletion after ECP treatment.

CONCLUSIONS:

ECP extends graft survival even in fully histoincompatible strain combinations with no immunosuppression. It increases the frequency of FoxP3(+)CD4(+)CD25(+) splenic T cells, and its effects can be transferred to untreated recipients using minimal numbers of CD4(+)CD25(+) T cells, indicating that CD4(+)CD25(+) T cells may play a key role in the immunomodulatory effects of ECP.

PMID:
18503960
DOI:
10.1016/j.healun.2008.02.015
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center