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 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.
Kassiotis
G
G
Institute for Immunology, Biomedical Sciences Research Center Alexander Fleming, Vari 166-72, Greece.
Kranidioti
K
K
Kollias
G
G
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005620:Freund's Adjuvant / Q000494:pharmacology; D015870:Gene Expression / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D037342:Pertussis Toxin; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000942:Antigens, Bacterial; D018122:B7-1 Antigen; D000949:Histocompatibility Antigens Class II; D014409:Tumor Necrosis Factor-alpha; D010566:Virulence Factors, Bordetella; D005620:Freund's Adjuvant; D037342:Pertussis Toxin