Defective CD4T cell priming and resistance to experimental autoimmune encephalomyelitis in TNF-deficient mice due to innate immune hypo-responsiveness

Abstract

We report here that tumor necrosis factor (TNF) deficiency causes innate hypo-responsiveness to a broad range of bacterial or viral constituents. In vivo hypo-responsiveness of TNF-deficient mice to mycobacteria results in defective CD4 + T cell priming to antigens administered in complete Freund's adjuvant (CFA). This deficiency is restored by supplementary mycobacteria. Furthermore, we show that even when self-reactive CD4 + T cell priming is fully restored, susceptibility of TNF-deficient mice to experimental autoimmune encephalomyelitis (EAE) depends on the co-administered pertussis toxin (PTx). TNF-deficient mice are completely resistant to EAE at sub-optimal doses of PTx, while supplementary PTx restores susceptibility. Therefore, TNF shows distinct functions in linking innate responsiveness to CD4 + T cell priming and to the induction of autoimmune disease.