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Transforming growth factor beta (TGFβ) plays a crucial role in prolonging allograft survival in an allodepletion ("pruning") skin transplant model.

Abstract：

:Adoptive cell therapies involving cell manipulation to achieve tolerance are increasingly being studied in animal models and in human trials. We have demonstrated that the specific removal of allo-stimulated dividing cells (or "pruning") promotes long-term allograft survival across a major MHC mismatch in transplant models including skin, heart and islet transplants. In this study, we examine the role of transforming growth factor beta (TGFβ), an important regulatory cytokine, on allograft survival in our allodepletion or "pruning" skin transplant model. Increased proliferation of CD4(+) T cells was observed following allo-stimulation of BALB/c spleen cells (labeled with CFSE) in the presence of the regulatory cytokines TGFβ and (interleukin-2) IL-2 in a mixed lymphocyte culture (MLC). Expression of the regulatory gene forkhead box-3 (FoxP3) was increased in both the allo-stimulated non-dividing (ND) (CFSE(high)) and dividing (D) (CFSE(low)) CD4(+) T cell populations, with the highest expression found in the D CD4(+) T cell population. Mice reconstituted with allo-stimulated ND CD4(+) T cells following TGFβ/IL-2 stimulation showed prolonged allograft survival, similar to previous data. Significantly, TGFβ/IL-2 stimulation prevented acute rejection of allografts across a major MHC mismatch in the presence of highly activated allo-stimulated D CD4(+) T cells. Blockade of TGFβ promoted rejection of allografts even following depletion of allo-stimulated D CD4(+) T cells. These studies support a crucial role for TGFβ in the survival of allografts and shows that regulatory cytokines TGFβ/IL2 can delay the rejection of allografts, even in the presence of highly activated alloreactive T cells.

journal_name

Transpl Immunol

journal_title

Transplant immunology

authors

Watson D,Zhang GY,Hu M,Wang YM,Fletcher J,Sartor M,Alexander SI

doi

10.1016/j.trim.2014.03.002

subject

Has Abstract

pub_date

2014-05-01 00:00:00

pages

168-77

issue

eissn

0966-3274

issn

1878-5492

pii

S0966-3274(14)00011-2

journal_volume

pub_type

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Transforming growth factor beta (TGFβ) plays a crucial role in prolonging allograft survival in an allodepletion ("pruning") skin transplant model.