SZ Ben-Sasson, J Hu-Li, J Quiel, S Cauchetaux, M Ratner, I Shapira, CA Dinarello, WE Paul. (2009). " IL-1 acts directly on CD4 T cells to enhance their antigen-driven expansion and differentiation. " Proc Natl Acad Sci U S A. 106, 7119-24. PMID: 19359475 DOI: 10.1073/pnas.0902745106
IL-1 causes a marked increase in the degree of expansion of naïve and memory CD4 T cells in response to challenge with their cognate antigen. The response occurs when only specific CD4 T cells can respond to IL-1beta, is not induced by a series of other cytokines and does not depend on IL-6 or CD-28. When WT cells are primed in IL-1R1(-/-) recipients, IL-1 increases the proportion of cytokine-producing transgenic CD4 T cells, especially IL-17- and IL-4-producing cells, strikingly increases serum IgE levels and serum IgG1 levels. IL-1beta enhances antigen-mediated expansion of in vitro primed Th1, Th2, and Th17 cells transferred to IL-1R1(-/-) recipients. The IL-1 receptor antagonist diminished responses to antigen plus lipopolysaccharide (LPS) by approximately 55%. These results indicate that IL-1beta signaling in T cells markedly induces robust and durable primary and secondary CD4 responses.