Involvement of CD28/CTLA4-B7 Costimulatory Pathway in the Development of Lymphadenopathy and Splenomegaly in MRL/lpr Mice

Journal of Veterinary Medical Science

Masaaki MURAKAMI²  Izumi NAKAGAWA²  Mitsuyoshi TAKIGUCHI¹  Noriko TOSA1²  Shunsuke CHIKUMA²  Mohammod Misanur RASHID²  Akira HASHIMOTO¹  Toshimitsu UEDE¹ 

[1] Laboratory of Pathobiology, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan;Section of Immunopathogenesis, Institute of Immunological Science, Hokkaido University, Sapporo 060-0815, Japan

关键词: costimulatory signal;    CTLA4IgG;    IL-4;    lymphadenopathy;    MRL/lpr;   

DOI  :  10.1292/jvms.62.29

学科分类：兽医学

来源: Japanese Society of Veterinary Science

【 摘 要 】

References(52)Cited-By(2)MRL/lpr mouse is an established animal model which develops autoimmune diseases including glomerulonephritis, sialoadenitis, hepatitis and inflammatory lung disease. Additionally, it has been reported that lpr strains uniquely accumulate CD3+CD4-CD8-B220+ (double negative, DN) T cells in lymphoid organs leading to lymphadenopathy and splenomegaly. To investigate the role of CD28/CTLA4-B7 pathway in the development of lymphadenopathy and splenomegaly, MRL/lpr mice were treated with soluble form of CTLA4 molecules, CTLA4IgG, which efficiently blocks this pathway. It was demonstrated that (i) the development of DN T cells was independent of the CD28/CTLA4-B7 pathway, (ii) the CD28/CTLA4-B7 pathway was required for the development of lymphadenopathy and splenomegaly, (iii) the CD28/CTLA4-B7 pathway was important for the accumulation of various cell populations in the lymph node and spleen, (iv) composition of the accumulating cell populations was not altered by CTLA4IgG treatment, and (v) activation of conventional T cells and IL-4 production from conventional T cells were the CD28/CTLA4-B7 pathway dependent. Thus, we concluded that the CD28/CTLA4-B7 pathway was required for the development of full-blown lymphadenopathy and splenomegaly in MRL/lpr mice.

【 授权许可】

Unknown