Faculty Collaboration Database

Ethylenecarbodiimide-coupled allogeneic antigen presenting cells induce human CD4+ regulatory T cells. Clin Immunol 2008 Dec;129(3):381-93

Date

09/30/2008

Pubmed ID

18819845

Pubmed Central ID

PMC3033601

DOI

10.1016/j.clim.2008.07.027

Scopus ID

2-s2.0-55549130238 (requires institutional sign-in at Scopus site)   2 Citations

Abstract

Adoptive transfer of naturally occurring CD4(+)CD25(+) regulatory T cells can tolerize transplantation alloresponses in animal models. However isolation of these cells in sufficient numbers from humans is cumbersome and prone to contamination with alloreactive CD25(+) T cells. Incubation of ethylenecarbodiimide-coupled antigen presenting cells (APC) with naïve T cells and antigen has been shown to induce tolerance in various experimental models. We therefore investigated whether ECDI-coupled allogeneic APC were able to induce an expandable human CD4(+) Treg population. CD4(+) and CD4(+) CD25(-) cells cultured for 5 days with ECDI-treated human PBMC exhibited potent suppressive capacity in a mixed lymphocyte reaction. Induction of these ECDI-Tregs was associated with up-regulation of Foxp3 mRNA and protein expression and they maintained high expression of CD62L and CD27 as well as low CD127 expression. ECDI-treated APC displayed reduced expression of the co-stimulatory signaling molecules CD40 and CD80, and failed to stimulate proliferation and cytokine secretion in co-cultured CD4(+) T cells. Restimulation in the presence of rapamycin and hrIL-2 led to expansion of ECDI-Tregs with increasing Foxp3 levels and suppressive activity significantly higher than expanded naturally occurring CD4(+)CD25(+) Tregs. In summary these findings support the hypothesis that ECDI-coupled APC can convert naïve CD4(+) T cells into functional Tregs with different phenotypic characteristics than naturally occurring CD4(+)CD25(+) Tregs. These inducible Tregs could provide a novel approach that might facilitate the translation of ex vivo generated and expanded Tregs into clinical settings.

Author List

Albert MH, Yu XZ, Magg T

Author

Xue-Zhong Yu MD Professor in the Microbiology and Immunology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Antigen-Presenting Cells
Carbodiimides
Coculture Techniques
Cytokines
Flow Cytometry
Forkhead Transcription Factors
Humans
Immune Tolerance
Leukocytes, Mononuclear
Lymphocyte Culture Test, Mixed
RNA, Messenger
Reverse Transcriptase Polymerase Chain Reaction
Sirolimus
T-Lymphocytes, Regulatory
Up-Regulation