@article{10.1172/jci.insight.90870, author = {Josephine R. Giles AND Adriana Turqueti Neves AND Ann Marshak-Rothstein AND Mark J. Shlomchik}, journal = {JCI Insight}, publisher = {The American Society for Clinical Investigation}, title = {Autoreactive helper T cells alleviate the need for intrinsic TLR signaling in autoreactive B cell activation}, year = {2017}, month = {2}, volume = {2}, url = {https://insight.jci.org/articles/view/90870}, abstract = {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.}, number = {4}, doi = {10.1172/jci.insight.90870}, url = {https://doi.org/10.1172/jci.insight.90870}, }