The H1-isoform of the cell surface receptor Slamf6 suppresses expansion of PD-1+ OPN+ CD4+ T Follicular Helper cells in the lupus-prone B6.Sle1b mice. (123.5)

Abstract A major role for the Slamf6 gene in the pathogenesis of lupus-related autoimmunity has been revealed by the analysis of a number of congenic mutant mouse strains. Importantly, upon introduction of one copy of a BAC transgene expressing the protein isoform Slamf6-H1 markedly ameliorates T cell-dependent lupus in the Sle1b mouse, which lacks H1. Here we report that a PD-1+ subset of memory CD4+ T cells dramatically expands in Sle1b mice, but not in Sle1b mice, which express Slamf6-H1. Further analysis showed that this PD-1+ population mainly consists of CXCR5+ T follicular helper cells the expansion of which is prevented by Slamf6-H1 as well as by the absence of the adapter SAP. Surprisingly, these T follicular helper cells express the cytokine osteopontin, which is known to drive polyclonal B cell proliferation. As the human osteopontin gene have been linked to the development of SLE, the outcomes of the present studies could suggest novel therapeutic modalities for SLE patients.