CD154 blockade modulates the ratio of Treg to Th1 cells and prolongs the survival of allogeneic corneal grafts in mice

Tan,Xiaobo; Zeng,Hui; Jie,Ying; Zhang,Yingnan; Xu,Qing; Pan,Zhiqiang

doi:10.3892/etm.2014.1527

CD154 blockade modulates the ratio of Treg to Th1 cells and prolongs the survival of allogeneic corneal grafts in mice

Authors:
- Xiaobo Tan
- Hui Zeng
- Ying Jie
- Yingnan Zhang
- Qing Xu
- Zhiqiang Pan
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Affiliations: Beijing Ophthalmology and Visual Science Key Laboratory, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, P.R. China, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100730, P.R. China
Published online on: February 7, 2014 https://doi.org/10.3892/etm.2014.1527
Pages: 827-834

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Abstract

Administration of anti-CD154 monoclonal antibody (mAb) may prolong the survival of an allograft; however, the associated therapeutic mechanisms remain poorly understood. This study aimed to evaluate the effects of anti-CD154 mAb on T‑cell responses in a mouse model of corneal allograft transplantation. BALB/c mice were transplanted with corneal grafts from C57BL/6 mice and treated intraperitoneally with 250 µg anti‑CD154 mAb or isotype IgG on days 0, 3 and 6 post surgery. The transparency of the corneal grafts was evaluated for potential rejection signs by slit‑lamp biomicroscopy and histopathology. The percentages of CD4+ T, Tim-3+CD4+ T helper (Th) 1 and CD4+CD25+Foxp3+ regulatory T cells (Tregs) in the spleen, ipsilateral draining lymph nodes and corneal grafts, and the frequency of splenic IFN-γ+ and IL-10+ expression in CD4+ T cells were determined by flow cytometry. Moreover, the ratio of Tregs to Th1 cells was calculated and the suppressive activity of splenic Tregs was measured. Anti‑CD154 neutralization significantly prolonged the survival of the corneal allograft (P=0.0012) and reduced the numbers of inflammatory infiltrates in the corneal graft. In the spleen and lymph nodes, anti-CD154 treatment reduced the frequency of CD4+ T cells, Tregs and particularly Th1 cells. In the corneal allografts, anti-CD154 treatment downregulated graft-infiltrated CD4+ T cells and Th1 cells, but increased graft‑infiltrated Tregs. Furthermore, anti-CD154 treatment increased the frequency of splenic IL-10+CD4+ T cells and decreased the concentration of splenic IFN-γ+CD4+ T cells. As a result, the ratio of Tregs to Th1 cells in the anti-CD154‑treated recipients increased. Anti‑CD154 treatment did not enhance the suppressive activity of Tregs in the recipients. The results indicate that the therapeutic effects of anti-CD154 mAb on prolonging the survival of the corneal allograft may be associated with an increased ratio of Tregs to Th1 cells in mice.

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