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Recurrent group A Streptococcus (GAS) tonsillitis and associated autoimmune diseases indicate that the immune response to this organism can be ineffective and pathological. TGF-[beta]1 is recognized as an essential signal for generation of regulatory T cells (Tregs) and T helper (Th) 17 cells. Here, the impact of TGF-[beta]1 induction on the T-cell response in mouse nasal-associated lymphoid tissue (NALT) following intranasal (i.n.) infections is investigated. ELISA and TGF-[beta]1-luciferase reporter assays indicated that persistent infection of mouse NALT with GAS sets the stage for TGF-[beta]1 and IL-6 production, signals required for promotion of a Th17 immune response. As predicted, IL-17, the Th17 signature cytokine, was induced in a TGF-[beta]1 signaling-dependent manner in single-cell suspensions of both human tonsils and NALT. Intracellular cytokine staining and flow cytometry demonstrated that [CD4.sup.+] IL-[17.sup.+] T cells are the dominant T cells induced in NALT by i.n. infections. Moreover, naive mice acquired the potential to clear GAS by adoptive transfer of [CD4.sup.+] T cells from immunized IL-[17A.sup.+/+] mice but not cells from IL-[17A.sup.-/-] mice. These experiments link specific induction of TGF-[beta]1 by a bacterial infection to an in vivo Th17 immune response and show that this cellular response is sufficient for protection against GAS. The association of a Th17 response with GAS infection reveals a potential mechanism for destructive autoimmune responses in humans. IL-17 | nasal-associated lymphoid tissue | Streptococcus pyogenes doi/10.1073/pnas.0904831107