¹Department of Immunology, Peking University Health Science Center, Peking University, 38 Xueyuan Rd, Beijing 100083, China

Correspondence: Xiao-Ming Gao, Tel: +86-10-82801156; Fax: +86-10-82801156 E-mail: xmgao@bjmu.edu.cn

Received 5 September 2006; Revised 26 November 2006; Accepted 6 December 2006.

Abstract

Systemic lupus erythematosus (SLE) is a typical autoimmune disease involving multiple systems and organs. Ample evidence suggests that autoreactive T cells play a pivotal role in the development of this autoimmune disorder. This study was undertaken to investigate the mechanisms of interaction between antigen presenting cells (APCs) and an autoreactive T cell (ATL1) clone obtained from lupus-prone BXSB mice. ATL1 cells, either before or after -ray irradiation, were able to activate naive B cells, as determined by B cell proliferation assays. Macrophages from BXSB mice were able to stimulate the proliferation of resting ATL1 cells at a responder/stimulator (R/S) ratio of 1/2.5. Dendritic cells (DCs) were much more powerful stimulators for ATL1 cells on a per cell basis. The T cell stimulating ability of macrophages and B cells, but not DCs, was sensitive to -ray irradiation. Monoclonal antibodies against mouse MHC-II and CD4 were able to block DC-mediated stimulation of ATL1 proliferation, indicating cognate recognition between ATL1 and APCs. Our data suggest that positive feedback loops involving macrophages, B cells and autoreactive T cells may play a pivotal role in keeping the momentum of autoimmune responses leading to autoimmune diseases.