Requirements for prolongation of allograft survival with regulatory T cell infusion in lymphosufficient hosts.

The Journal of Surgical Research
T V BrennanSang-Mo Kang

Abstract

For the clinical applicability of regulatory T cells (Tregs) in transplantation, it is critical to determine if donor antigen specificity is required for their immunosuppressive function. We developed an allospecific CD4(+) T cell receptor transgenic (TCR-tg) mouse as a source for large numbers of Tregs with defined allospecificity and tested whether they are more effective than polyclonal Tregs at suppressing allograft rejection. CD4(+)CD25(+)CD62L(hi) T cells were sorted from the spleen and peripheral lymph nodes of wild-type (WT-Tregs) and TCR-tg (Allo-Tregs) mice, and expanded using IL-2 and anti-CD3/anti-CD28 conjugated magnetic beads. Tregs were tested for their ability to suppress the proliferation and cytokine production of alloreactive CD4(+)CD25(-) T cells in mixed leukocyte assays. Syngeneic WT hosts were adoptively transferred 5 × 10(6) Tregs and transplanted with allogeneic hearts. Using anti-CD3/anti-CD28 conjugated beads, Tregs were expanded in vitro 100-fold and maintained their suppressor phenotype and function. Allo-Tregs were 6-8 times more potent on a cell-for-cell basis than WT-Tregs in suppressing allospecific proliferation in vitro. Allo-Tregs were unable to suppress in the absence of allo-antigen. Adopti...Continue Reading

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Citations

Dec 16, 2011·Journal of Molecular Cell Biology·Qizhi TangSang-Mo Kang
Sep 10, 2014·The Journal of Clinical Investigation·Geoffrey CamirandDavid M Rothstein
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Feb 15, 2019·Cellular & Molecular Immunology·Pawan K GuptaMaria-Luisa Alegre
Jan 21, 2020·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Antoine SicardMegan K Levings
Sep 21, 2019·Immunological Reviews·Shuangjin YuXunrong Luo
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Oct 15, 2014·Current Opinion in Organ Transplantation·Qizhi Tang, Sang-Mo Kang
Jul 14, 2012·Current Opinion in Organ Transplantation·Qizhi Tang, Karim Lee
Mar 13, 2021·Frontiers in Immunology·Marta FortunatoSilvia Gregori
Apr 6, 2021·Current Transplantation Reports·Johanna C Wagner, Qizhi Tang

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