Complement component 3 deficiency prolongs MHC-Ⅱ disparate allograft survival by increasing the population of CD4~+ CD25~+ regulatory T cells
详细信息 查看官网全文
- 英文论文题名：Complement component 3 deficiency prolongs MHC-Ⅱ disparate allograft survival by increasing the population of CD4~+ CD25~+ regulatory T cells
- 论文作者：Zheng Quanyou ; Zhang Keqin ; Xu Guilian
- 英文论文作者：Zheng Quanyou ; Zhang Keqin ; Xu Guilian ; Department of Nephrology ; Southwest Hospital ; Third Military Medical University ; Department of Immunology ; Third Military Medical University
- 年：2016
- 作者机构：Department of Nephrology,Southwest Hospital,Third Military Medical University;Department of Immunology,Third Military Medical University;
- 英文论文关键词：Complement component 3 ; Regulatory T cells ; Allograft rejection
- 会议召开时间：2016-11-04
- 会议录名称：第十一届全国免疫学学术大会摘要汇编
- 英文会议录名称：Abstracts of 2016 CSI Congress on Immunology
- 语种：英文
- 分类号：R392
- 学会代码：IGMD
- 会议名称：第十一届全国免疫学学术大会
- 会议地点：中国安徽合肥
- 主办单位：中国免疫学会
- 学会名称：中国免疫学会
- 页数：2
- 文件大小：1354k
- 原文格式：D
- 会议级别：全国
摘要
Objective: Recent reports suggest that both the complement system and alloreactive T cells contribute to allograft rejection. However, their underlying relationship and mechanism of action is poorly understood. Herein, we investigate the role of complement component 3(C3) in a single MHC- Ⅱ molecule mismatched murine model of allograft rejection using C3 deficient mice(C3~(-/-)) as skin graft donors or recipients.Methods: The allografts survival were monitored and histological changes of skin grafts were also assessed. Gene expression coding inflammatory cytokines and T cell proliferation in vitro were tested. The expansion of CD4~+CD25~+Foxp3~+ regulatory T cells and Th1/17 cells were analyzed by Flow cytometry and immune histological staining. At last, the DC capacity was examined by co-cluture them with allo-reactive CD4~+T cells for up to 9 days.Results: Compared with C3~+/~+ B6 allografts, C3~(-/-) B6 grafts dramatically prolonged survival in MHC-Ⅱ molecule mismatched H-2bm12 B6 recipients. However, no difference was observed when H-2bm12 B6 skin grafts were donated to C3~+/~+ B6 and C3~(-/-) B6 recipients. Compared with C3~+/~+ allografts, both Th17 cell infiltration and Th1/Th17 associated cytokine mR NA levels were clearly reduced in C3~(-/-) allografts. Moreover, C3~(-/-) allografts caused an impaired mixed lymphocyte reaction and attenuated Th1/Th17 responses, but increased CD4~+CD25~+Foxp3~+ regulatory T(Treg) cell expression markedly in local intragraft and H-2bm12 recipients. Depletion of Treg cells by anti-CD25 monoclonal antibody(m Ab) negated the survival advantages conferred by C3 deficiency. Additionally, C3~(-/-) dendritic cells(DC) had more advantage in upregulating Foxp3 gene expression and Treg cell induction compared to C3~+/~+ DC.Conclusion: Our results indicate for the first time that local C3 deficiency can prolong MHC-Ⅱ molecule mismatched skin allograft survival and confirm the association of local C3 deficiency with CD4~+ CD25~+ Treg cell population expansion, which may then lead to impaired Th1/Th17 responses in recipients with C3~(-/-) allografts.
Objective: Recent reports suggest that both the complement system and alloreactive T cells contribute to allograft rejection. However, their underlying relationship and mechanism of action is poorly understood. Herein, we investigate the role of complement component 3(C3) in a single MHC- Ⅱ molecule mismatched murine model of allograft rejection using C3 deficient mice(C3~(-/-)) as skin graft donors or recipients.Methods: The allografts survival were monitored and histological changes of skin grafts were also assessed. Gene expression coding inflammatory cytokines and T cell proliferation in vitro were tested. The expansion of CD4~+CD25~+Foxp3~+ regulatory T cells and Th1/17 cells were analyzed by Flow cytometry and immune histological staining. At last, the DC capacity was examined by co-cluture them with allo-reactive CD4~+T cells for up to 9 days.Results: Compared with C3~+/~+ B6 allografts, C3~(-/-) B6 grafts dramatically prolonged survival in MHC-Ⅱ molecule mismatched H-2bm12 B6 recipients. However, no difference was observed when H-2bm12 B6 skin grafts were donated to C3~+/~+ B6 and C3~(-/-) B6 recipients. Compared with C3~+/~+ allografts, both Th17 cell infiltration and Th1/Th17 associated cytokine mR NA levels were clearly reduced in C3~(-/-) allografts. Moreover, C3~(-/-) allografts caused an impaired mixed lymphocyte reaction and attenuated Th1/Th17 responses, but increased CD4~+CD25~+Foxp3~+ regulatory T(Treg) cell expression markedly in local intragraft and H-2bm12 recipients. Depletion of Treg cells by anti-CD25 monoclonal antibody(m Ab) negated the survival advantages conferred by C3 deficiency. Additionally, C3~(-/-) dendritic cells(DC) had more advantage in upregulating Foxp3 gene expression and Treg cell induction compared to C3~+/~+ DC.Conclusion: Our results indicate for the first time that local C3 deficiency can prolong MHC-Ⅱ molecule mismatched skin allograft survival and confirm the association of local C3 deficiency with CD4~+ CD25~+ Treg cell population expansion, which may then lead to impaired Th1/Th17 responses in recipients with C3~(-/-) allografts.
Objective: Recent reports suggest that both the complement system and alloreactive T cells contribute to allograft rejection. However, their underlying relationship and mechanism of action is poorly understood. Herein, we investigate the role of complement component 3(C3) in a single MHC- Ⅱ molecule mismatched murine model of allograft rejection using C3 deficient mice(C3~(-/-)) as skin graft donors or recipients.Methods: The allografts survival were monitored and histological changes of skin grafts were also assessed. Gene expression coding inflammatory cytokines and T cell proliferation in vitro were tested. The expansion of CD4~+CD25~+Foxp3~+ regulatory T cells and Th1/17 cells were analyzed by Flow cytometry and immune histological staining. At last, the DC capacity was examined by co-cluture them with allo-reactive CD4~+T cells for up to 9 days.Results: Compared with C3~+/~+ B6 allografts, C3~(-/-) B6 grafts dramatically prolonged survival in MHC-Ⅱ molecule mismatched H-2bm12 B6 recipients. However, no difference was observed when H-2bm12 B6 skin grafts were donated to C3~+/~+ B6 and C3~(-/-) B6 recipients. Compared with C3~+/~+ allografts, both Th17 cell infiltration and Th1/Th17 associated cytokine mR NA levels were clearly reduced in C3~(-/-) allografts. Moreover, C3~(-/-) allografts caused an impaired mixed lymphocyte reaction and attenuated Th1/Th17 responses, but increased CD4~+CD25~+Foxp3~+ regulatory T(Treg) cell expression markedly in local intragraft and H-2bm12 recipients. Depletion of Treg cells by anti-CD25 monoclonal antibody(m Ab) negated the survival advantages conferred by C3 deficiency. Additionally, C3~(-/-) dendritic cells(DC) had more advantage in upregulating Foxp3 gene expression and Treg cell induction compared to C3~+/~+ DC.Conclusion: Our results indicate for the first time that local C3 deficiency can prolong MHC-Ⅱ molecule mismatched skin allograft survival and confirm the association of local C3 deficiency with CD4~+ CD25~+ Treg cell population expansion, which may then lead to impaired Th1/Th17 responses in recipients with C3~(-/-) allografts.
引文