Xenoreactive CD4+ memory T cells resist inhibition by anti-CD44 mAb and reject islet grafts via a Th2-dependent pathway
Autor: | Qi Zhu, Ruxin Huang, Panpan Cheng, Helong Dai, Wei Shao, Jibing Chen, F. Wang, Feng Wang, Junjie Xia, Yuanzheng Peng, Zhongquan Qi |
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Rok vydání: | 2011 |
Předmět: |
Transplantation
geography geography.geographical_feature_category biology business.industry medicine.drug_class Xenotransplantation medicine.medical_treatment Immunology CD44 Monoclonal antibody Islet Molecular biology Isotype medicine biology.protein Interferon gamma Antibody business medicine.drug |
Zdroj: | Xenotransplantation. 18:252-261 |
ISSN: | 0908-665X |
Popis: | Peng YZ, Chen JB, Shao W, Wang FY, Dai HL, Cheng PP, Xia JJ, Wang F, Huang R, Zhu Q, Qi Z. Xenoreactive CD4+ memory T cells resist inhibition by anti-CD44 mAb and reject islet grafts via a Th2-dependent pathway. Xenotransplantation 2011; 18: 252–261. © 2011 John Wiley & Sons A/S. Abstract: Background: Memory T cells are a significant barrier to the induction of transplant tolerance. Our previous study demonstrated that multiple applications of anti-CD44 monoclonal antibody (mAb) could significantly inhibit CD4+ memory T cells from mediating rejection of cardiac allografts. Now, we sought to explore the effect and mechanism of anti-CD44 mAb on the rejection of islet allografts and xenografts mediated by CD4+ memory T cells. Methods: In this study, we first engrafted skin grafts of C57BL/6 (B6) mice or Dark Agouti (DA) rats onto BALB/c mice to induce donor-reactive memory T cells. We adoptively transferred purified CD4+ memory T cells to BALB/c origin nude mice and then transplanted islet allografts and xenografts to produce the Allo-Tx and Xeno-Tx models, respectively. We subsequently administered multiple anti-CD44 mAb and observed changes in the survival times of the islet grafts. Results: In the Allo-Tx model, the mean survival time (MST) of the grafts was 7.7 days in the isotype group, and 20.3 days in the anti-CD44 group. In the Xeno-Tx model, the MST of the grafts was 7.2 days in the isotype group and 8.2 days in the anti-CD44 group. Compared with the isotype group, CD4+ T cells on the grafts in the anti-CD44 group were significantly decreased in both the Allo-Tx and Xeno-Tx models, but the proportion of CD4+ memory T cells in the spleens and draining lymph nodes of the recipient nude mice in the anti-CD44 group was significantly decreased in the Allo-Tx model, while it was increased in the Xeno-Tx model. The production of donor-specific IgG antibody in the anti-CD44 group did not vary in the Allo-Tx model, while it was markedly elevated in the Xeno-Tx model. Furthermore, the expression of interferon gamma in the anti-CD44 group was markedly decreased in both the Allo-Tx and Xeno-Tx models, while the expression of IL-4 in the anti-CD44 group was significantly increased only in the Xeno-Tx model. Conclusion: Multiple applications of the anti-CD44 mAb could significantly inhibit donor-reactive CD4+ memory T cells from rejecting grafts via a Th1-dependent pathway, but xenoreactive CD4+ memory T cells can avoid the effects of anti-CD44 mAb to reject islet xenografts via a Th2-dependent pathway. |
Databáze: | OpenAIRE |
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