CD28/B7 CO‐STIMULATION REGULATES MEMORY CD4 T CELL RESPONSES TO INFLUENZA VIRUS INFECTION

Abstract

The host immune response to many viral infections is often accompanied by immunopathology. We have established that memory CD4 T cells specific for influenza virus hemagglutinin (HA) facilitates viral clearance in the context of increased weight loss and lung mononuclear cell infiltration. Work in the lab demonstrated that the CD28/B7 co‐stimulatory pathway alters cytokine production, expansion and subset distribution of antigen‐specific memory CD4 T cells upon recall. We hypothesized that modulation of the memory CD4 T cell response by blocking CD28/B7 might optimize protection to influenza virus challenge. To test this hypothesis we adoptively transferred HA ‐specific memory CD4 T cells into naive BALB/c mice, which were treated with CTLA4Ig or IgG2a control and infected with influenza virus PR8 (A/PR8/34). Interestingly, CTLA4Ig treatment modestly inhibited CD4 memory‐mediated viral clearance; however, CTLA4‐Ig treated hosts exhibited significant reduction in weight loss. Treatment with CTLA4Ig also resulted in a shift of the memory CD4 T cells to a predominantly CD62Lhi central memory phenotype accompanied by inhibition of recruitment of memory and endogenous CD4 T cells to infected lungs. These results suggest that blocking the CD28/B7 co‐stimulatory pathway controls memory‐mediated responses to influenza by limiting pathology while maintaining protection.