Abstract
Abstract Upon activation CD4 T cells differentiate into different subsets that have distinct functions in the immune response. Antigen presentation in the presence of co-stimulation and cytokines is required for optimal CD4 T cell activation and differentiation. Cytokines play a well-described crucial role driving CD4 T cell differentiation, but the role of different antigen presenting cells and co-stimulation remains relatively unexplored. To address this question we developed mice that lack B7-1 expression on B cells or on dendritic cells (DCs), on a B7-2 deficient background. CD4 differentiation was studied in the context of acute lymphocytic choriomeningitis virus (LCMV) infection. We find that mice lacking B7-1 on DCs have a profound defect on virus-specific CD4 T cell expansion that affects Th1 and Tfh numbers, but with the most drastic reduction in Th1 differentiation. In contrast, mice lacking B7-1 on B cells have similar numbers of LCMV-specific CD4 T cells as control mice. However, even though CXCR5 expressing LCMV-specific CD4 T cells numbers appear unaffected by B7-1 deficiency on B cells, there was a reduction in cells expressing high levels of CXCR5, PD-1 and Bcl-6 and a profound defect in LCMV-specific long lived plasma cells and antibodies. We conclude that CD4 T cell differentiation requires cell-type specific co-stimulation, and co-stimulation by B cells is essential to obtain functional Tfh and long-term humoral responses after acute viral infection.
Published Version
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