Quantifying the magnitude of antigen-specific CD4 T cell responses (39.27)

Abstract

CD4 T cells play a vital role in orchestrating adaptive immune responses. Measuring the magnitude of the CD4 T cell response to a given pathogen is currently hindered by the lack of complete knowledge of all of the CD4 T cell epitopes. In cases where most or all of the CD4 T cell epitopes have been mapped, current estimates based on intracellular cytokine production for cytokines such as IFN-γ may also under-represent the frequency of antigen-specific CD4 T cells because of the high heterogeneity in cytokine production exhibited by differentiated effector CD4 T cells. Here we show that following lymphocytic choriomeningitis virus (LCMV) infection, T cell receptor-transgenic CD4 T cells specific to LCMV upregulate CD11a and CD49d and that expression of these adhesion molecules remains stable into memory. Expression of these integrins requires cognate antigen and is not modulated non-specifically by inflammatory signals such as stimulation with LPS or CPG. Additionally, CD11a and CD49d expression is upregulated on endogenous CD4 T cells following acute LCMV infection as well as all LCMV-specific CD4 T cells that respond to previously identified CD4 T cell epitopes. Using these markers we estimate the total magnitude of the virus-specific CD4 T cell response to multiple pathogens and our results indicate that the CD4 T cell response is substantially larger than previously thought.