Robust antigen specific th17 t cell response to group a streptococcus is dependent on il-6 and intranasal route of infection

Group a streptococcus (gas,streptococcus pyogenes) is the cause of a variety of clinical conditions,ranging from pharyngitis to autoimmune disease. peptide-major histocompatibility complex class ii (pmhcii) tetramers have recently emerged as a highly sensitive means to quantify pmhcii-specific cd4 + helper t cells and evaluate their contribution to both protective immunity and autoimmune complications induced by specific bacterial pathogens. in lieu of identifying an immunodominant peptide expressed by gas,a surrogate peptide (2w) was fused to the highly expressed m1 protein on the surface of gas to allow in-depth analysis of the cd4 + helper t cell response in c57bl/6 mice that express the i-a b mhcii molecule. following intranasal inoculation with gas-2w,antigen-experienced 2w:i-a b-specific cd4 + t cells were identified in the nasal-associated lymphoid tissue (nalt) that produced il-17a or il-17a and ifn-γ if infection was recurrent. the dominant th17 response was also dependent on the intranasal route of inoculation; intravenous or subcutaneous inoculations produced primarily ifn-γ + 2w:i-a b+ cd4 + t cells. the acquisition of il-17a production by 2w:i-a b-specific t cells and the capacity of mice to survive infection depended on the innate cytokine il-6. il-6-deficient mice that survived infection became long-term carriers despite the presence of abundant ifn-γ-producing 2w:i-a b-specific cd4 + t cells. our results suggest that an imbalance between il-17- and ifn-γ-producing cd4 + t cells could contribute to gas carriage in humans. © 2011 dileepan et al.