Autoreactive helper T cells alleviate the need for intrinsic TLR signaling in autoreactive B cell activation
Department of Medicine, Division of Rheumatology
Immune System Diseases | Immunology and Infectious Disease
T cells play a significant role in the pathogenesis of systemic autoimmune diseases, including systemic lupus erythematosus; however, there is relatively little information on the nature and specificity of autoreactive T cells. Identifying such cells has been technically difficult because they are likely to be rare and low affinity. Here, we report a method for identifying autoreactive T cell clones that recognize proteins contained in autoantibody immune complexes, providing direct evidence that functional autoreactive helper T cells exist in the periphery of normal mice. These T cells significantly enhanced autoreactive B cell proliferation and altered B cell differentiation in vivo. Most importantly, these autoreactive T cells were able to rescue many aspects of the TLR-deficient AM14 (anti-IgG2a rheumatoid factor) B cell response, suggesting that TLR requirements can be bypassed. This result has implications for the efficacy of TLR-targeted therapy in the treatment of ongoing disease.
DOI of Published Version
JCI Insight. 2017 Feb 23;2(4):e90870. doi: 10.1172/jci.insight.90870. Link to article on publisher's site
Giles, Josephine R.; Neves, Adriana Turqueti; Marshak-Rothstein, Ann; and Shlomchik, Mark J., "Autoreactive helper T cells alleviate the need for intrinsic TLR signaling in autoreactive B cell activation" (2017). Open Access Articles. 3088.