Toxin-neutralizing Abs are associated with improved T cell function following recovery from Staphylococcus aureus infection

BACKGROUND. T cell responses are impaired in Staphylococcus aureus-infected children, highlighting a potential mechanism of immune evasion. This study tested the hypotheses that toxin -specific antibodies protect immune cells from bacterial killing and are associated with improved T cell function following infection. METHODS. S. aureus-infected and healthy children (N = 33 each) were prospectively enrolled. During acute infection and convalescence, we quantified toxin -specific IgG levels by ELISA, antibody function using a cell killing assay, and functional T cell responses by ELISPOT. RESULTS. There were no differences in toxin -specific IgG levels or ability to neutralize toxinmediated immune cell killing between healthy and acutely infected children, but antibody levels and function increased following infection. Similarly, T cell function, which was impaired during acute infection, improved following infection. However, the response to infection was highly variable; up to half of children did not have improved antibody or T cell function. Serum from children with higher alpha-hemolysin-specific IgG levels more strongly protected immune cells against toxin -mediated killing. Importantly, children whose serum more strongly protected against toxinmediated killing also had stronger immune responses to infection, characterized by more elicited antibodies and greater improvement in T cell function following infection. CONCLUSION. This study demonstrates that, despite T cell impairment during acute infection, S. aureus elicits toxin -neutralizing antibodies. Individual antibody responses and T cell recovery are variable. These findings also suggest that toxin -neutralizing antibodies protect antigen -presenting cells and T cells, thereby promoting immune recovery. Finally, failure to elicit toxin -neutralizing antibodies may identify children at risk for prolonged T cell suppression. FUNDING. NIH National Institute of Allergy and Infectious Diseases R01AI125489 and Nationwide Children's Hospital.