Critical influence of natural regulatory CD25+ T cells on the fate of allografts in the absence of immunosuppression.

Abstract:

BACKGROUND:Allografts are occasionally accepted in the absence of immunosuppression. Because naturally occurring CD4(+)CD25(+) regulatory T cells (natural CD25(+) Treg cells) have been shown to inhibit allograft rejection, we investigated their influence on the outcome of allografts in nonimmunosuppressed mouse recipients. METHODS:We compared survival times of male CBA/Ca skin grafts in female CBA/Ca recipients expressing a transgenic anti-HY T-cell receptor on a RAG-1(+/+) (A1[M]RAG+) or a RAG-1(-/-) (A1[M]RAG-) background. Depletion of natural CD25(+) Treg cells in A1[M]RAG+ mice was achieved by in vivo administration of the PC61 monoclonal antibody. The influence of natural CD25(+) Treg cells on the fate of major histocompatibility complex class II-mismatched (C57BL/6X bm12)F1 skin or bm12 heart transplants in C57BL/6 recipients was also assessed. Finally, we investigated the impact of natural CD25(+) Treg cells on the production of T-helper (Th)1 and Th2 cytokines in mixed lymphocyte cultures between C57BL/6 CD4(+) CD25(-) T cells as responders and bm12 or (C57BL/6X bm12)F1 antigen-presenting cells as stimulators. RESULTS:Male allografts were spontaneously accepted by female A1(M)RAG+ mice but readily rejected by female A1(M)RAG+ mice depleted of natural CD25(+) Treg cells by pretreatment with the PC61 monoclonal antibody. Depletion of CD25(+) Treg cells also enhanced eosinophil-determined rejection of (C57BL/6X bm12)F1 skin grafts or bm12 cardiac grafts in C57BL/6 recipients. Finally, natural CD25(+) Treg cells inhibited the production of interleukin (IL)-2, interferon-gamma, IL-5, and IL-13 in mixed lymphocyte culture in a dose-dependent manner. CONCLUSION:Natural CD25(+) Treg cells control Th1- and Th2-type allohelper T-cell responses and thereby influence the fate of allografts in nonimmunosuppressed recipients.

journal_name

Transplantation

journal_title

Transplantation

authors

Benghiat FS,Graca L,Braun MY,Detienne S,Moore F,Buonocore S,Flamand V,Waldmann H,Goldman M,Le Moine A

doi

10.1097/01.tp.0000155179.61445.78

subject

Has Abstract

pub_date

2005-03-27 00:00:00

pages

648-54

issue

6

eissn

0041-1337

issn

1534-6080

pii

00007890-200503270-00009

journal_volume

79

pub_type

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