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Immunity. 2002 May;16(5):719-32.

CD154-dependent priming of diabetogenic CD4(+) T cells dissociated from activation of antigen-presenting cells.

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Department of Microbiology and Infectious Diseases and Julia McFarlane Diabetes Research Center, The University of Calgary, Faculty of Medicine, 3330 Hospital Drive N.W., Calgary, Alberta, Canada T2N 4N1.


We followed the fate of K(d)- or I-A(g7)-restricted beta cell-autoreactive T cells in monoclonal TCR-transgenic NOD mice expressing or lacking CD154. 8.3-NOD.RAG-2(-/-)/CD154(-/-) mice, which bear autoreactive CD8(+) T cells, developed diabetes with the same incidence and tempo as 8.3-NOD.RAG-2(-/-)/CD154(+) mice. Recruitment of CD154(-/-) 8.3-CD8(+) CTL was accelerated by CD154(+)CD4(+) T cells, by expression of a B7.1 transgene in beta cells or by treatment of the mice with CpG-DNA or an agonistic anti-CD40 antibody. In contrast, the autoreactive CD4(+) T cells maturing in 4.1-NOD.RAG-2(-/-) mice lost their diabetogenic potential if they lacked CD154, even in the presence of CD154(+)CD4(+) T cells, B7.1 molecules on beta cells, CpG-DNA treatment, or systemic CD40 ligation. These results demonstrate the existence of a novel, CD154-dependent pathway of CD4(+) T cell activation that is independent of CD40-mediated activation of APCs.

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