Interleukin (IL)-35 is raising our expectations.

PURPOSE: To elucidate and discuss the role of IL-35 in immunity to parasitic and bacterial infections as well as in autoimmunity in terms of its anti-inflammatory properties, we highlight significant findings on this novel member of the IL-12 family. METHODS: Studies using genetically deficient mice have greatly enhanced our understanding of the biology of IL-35. On the basis of data derived from the analysis of these genetically deficient mice published by NIH, we focus on the key features of this heterodimeric cytokine, especially its relation to the other IL-12 family members, and discuss its potential relevance to the clinical usage. PRINCIPAL FINDINGS: IL-35 is required for the CD4+CD25+ Treg cells-mediated immune regulation, the alleviation of some inflammatory responses, as well as the expansion of CD4+CD25- Teff cells simultaneously. Moreover, administration or augmentation of IL-35 suppresses some diseases of autoimmune or allergic origin like collagen-induced arthritis or Helicobacter-induced colitis in animal models, demonstrating its potential in therapy of diseases mediated by inflammatory cytokines. However, some questions involving it are still unclear, including the composition of IL-35 receptor, IL-35-related cell signaling pathway, the different expression patterns of IL-35 between human and murine T cells, etc. CONCLUSION: As our understanding of the IL-35 is rapidly growing and changing, it will bring us more therapeutic strategies towards some intractable immune diseases such as Lupus Erythematosus.

OX40-mediated differentiation to effector function requires IL-2 receptor signaling but not CD28, CD40, IL-12Rbeta2, or T-bet.

Ag-specific CD4 T cells transferred into unirradiated Ag-bearing recipients proliferate, but survival and accumulation of proliferating cells is not extensive and the donor cells do not acquire effector functions. We previously showed that a single costimulatory signal delivered by an agonist Ab to OX40 (CD134) promotes accumulation of proliferating cells and promotes differentiation to effector CD4 T cells capable of secreting IFN-gamma. In this study, we determined whether OX40 costimulation requires supporting costimulatory or differentiation signals to drive acquisition of effector T cell function. We report that OX40 engagement drives effector T cell differentiation in the absence of CD28 and CD40 signals. Two important regulators of Th1 differentiation, IL-12R and T-bet, also are not required for acquisition of effector function in CD4 T cells responsive to OX40 stimulation. Finally, we show that CD25-deficient CD4 T cells produce little IFN-gamma in the presence of OX40 costimulation compared with wild type, suggesting that IL-2R signaling is required for efficient OX40-mediated differentiation to IFN-gamma secretion.