title: Effect of cytotoxic T-lymphocyte-associated protein 4 on CD4(+)CD25(+) regulatory T cells in murine schistosomiasis japonica.
abstract: In a previous study we demonstrated that CD4(+)CD25(+) regulatory T cells (Tregs) contributed to the escape of Schistosoma japonicum (S. japonicum) from the host's immune responses. In this paper, we studied the effect of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) on CD4(+)CD25(+) Tregs in murine Schistosomiasis japonica and its corresponding role in the immune evasion of S. japonicum in mice. The results showed substantial reductions of worm burden and egg production in worm groups treated with anti-CD25 or anti-CTLA-4 monoclonal antibodies (mAb) compared to an infected but untreated control. The reduction effect was even enhanced in an experimental group co-treated with both mAbs. Compared to the control group, the percentage of CD4(+)CD25(+) Tregs was very much lower in the anti-CD25 mAb group as determined by FACS analyses and higher in the anti-CTLA-4 mAb group. ELISA analyses showed that both the anti-CTLA-4 mAb and the co-treated groups had higher levels of cytokines compared to the control group as well as larger egg granuloma sizes as determined by microscopical analyses of liver sections of infected mice. These results suggest that treatment with an anti-CTLA-4 mAb allows the host to clear S. japonicum, but at the cost of elevated pathological damage. The latter indicated a role of CTLA-4 in granuloma formation. Moreover, CD4(+)CD25(+) Tregs and CTLA-4 may exert synergistic effects during immune evasion processes by enhancing Th1-type immune response.
authors.affiliation: Department of Clinical Laboratory, Wuchang Hospital, No. 116 Yangyuan Street, Wuhan 430063, China. Electronic address: tangchunlina@yahoo.com.cn.
authors.forename: Chun-Lian
authors.initials: CL
authors.lastname: Tang
authors.affiliation: Department of Parasitology, Tongji Medical College, Huazhong University of Science and Technology, No. 13 Hangkong Road, Wuhan 430030, China.
authors.forename: Jia-Hui
authors.initials: JH
authors.lastname: Lei
authors.affiliation: Department of Parasitology, Tongji Medical College, Huazhong University of Science and Technology, No. 13 Hangkong Road, Wuhan 430030, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Guan
authors.affiliation: Department of Parasitology, Tongji Medical College, Huazhong University of Science and Technology, No. 13 Hangkong Road, Wuhan 430030, China.
authors.forename: Yong-Long
authors.initials: YL
authors.lastname: Li
authors.affiliation: School of Public Health, Peking University, Beijing 100191, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Liu
authors.affiliation: Institute for Parasitology, Justus-Liebig-University, 35392 Giessen, Germany.
authors.forename: Christoph G
authors.initials: CG
authors.lastname: Grevelding
authors.affiliation: Department of Parasitology, Medical College of Wuhan University, Wuhan 430071, China.
authors.forename: Ming-Sen
authors.initials: MS
authors.lastname: Jiang
authors.affiliation: Department of Parasitology, Medical College of Wuhan University, Wuhan 430071, China.
authors.forename: Hui-Fen
authors.initials: HF
authors.lastname: Dong
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D060908:CTLA-4 Antigen / Q000276:immunology*; D016207:Cytokines / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D057131:Immune Evasion; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D008099:Liver / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D011897:Random Allocation; D012549:Schistosoma japonicum / Q000276:immunology*; D012554:Schistosomiasis japonica / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D060908:CTLA-4 Antigen; D016207:Cytokines; D053645:Interleukin-2 Receptor alpha Subunit
keywords: CD4(+)CD25(+) Tregs; CTLA-4; Cytokines; Immune evasion; Schistosoma japonicum