Aberrant expansion of CXCR5+ memory CD4 T cells in patients with systemic lupus erythematosus
© Choi et al.; licensee BioMed Central Ltd. 2014
Published: 18 September 2014
Autoreactive B cells in SLE undergo autoantigen selection, suggesting a requirement for germinal center follicular helper T (Tfh) cells in their maturation. However, evidence for dysregulation of Tfh cells in SLE and their potential contribution to disease remains unclear. Recently, blood CXCR5+ CD4 T cells, a heterogeneous pool consisting of functionally distinct Th1-like, Th2-like, and Th17-like subsets, have been proposed to be the circulating (blood) memory Tfh cells. We hypothesized that expanded CXCR5+ memory cells in the blood of human lupus patients promote B-cell helper function reflecting the abnormal T-B-cell responses in secondary lymphoid organs.
Methods and results
We characterized such cells in SLE patients by flow cytometry and T-B coculture studies. SLE patients had significant expansion of CXCR5+ICOShiPD-1hi CD4 T cells compared with controls. Such cells were Bcl6-, but robustly expressed IL-21 with a portion Ki-67+, indicating their functional activity. The blood cells were capable of providing blood-born memory B cells with survival and differentiation signals to secrete isotype switched Igs, including antinuclear antibodies.
We speculate that therapies which alter T-B collaboration in lupus will abrogate their expansion, accompanied by reduced autoantibody titers and improved disease activity in SLE patients. Our results suggest that aberrant T-B collaboration in lupus is critical to disease pathogenesis and its blockade is likely to be important therapeutically.
This work was supported in part by the Alliance for Lupus Research and AR040072, AR44076, AR062842, and AR053495 (to JC). STK was supported by a Research Scientist Development Award from the American College of Rheumatology Research and Education Foundation and by T32 AR07107.
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