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

We report here that tumor necrosis factor (TNF) deficiency causes innate hy po-responsiveness to a broad range of bacterial or viral constituents. In v ivo hypo-responsiveness of TNF-deficient mice to mycobacteria results in de fective 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 autoi mmune encephalomyelitis (EAE) depends on the co-administered pertussis toxi n (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 c ell priming and to the induction of autoimmune disease. (C) 2001 Elsevier S cience BN. All rights reserved.