Epitope-Specific Regulatory T cells Differentially Modulate the CD8 T Cell Response to Respiratory Syncytial Virus in Mice (45.29)

Abstract

RSV infection is the leading cause of lower respiratory disease in infants and young children, accounting for >120,000 hospitalizations each year in the US alone. Although CD8 T cell effector function is key to virus clearance, CD4 T cells coordinate the immune response and can lead to immunopathology. Therefore, they play a central role in the immunity and immunopathogenesis of RSV infection.

To facilitate in depth evaluation of RSV-induced CD4 T cell responses we identified two new I-A^b- restricted dominant CD4 T cell epitopes, M_213-223 and M2_27-37, in RSV M and M2 that also contain well characterized CD8 T cell epitopes. CD4 T cells from lung and spleen of RSV-infected CB6F1 mice produce different patterns of IL-2, IFN-γ and other cytokines after peptide stimulation. Novel tetrameric peptide-I-A^b complexes identified 0.5% and 1.6% RSV M- and M2-specific CD4 T cells in lungs of the infected mice. Peptide-stimulated CD4 T cells produced different patterns of regulation on CD8 T cell responses to RSV M and M2 epitopes in vitro. The regulatory function of the CD4 T cell correlated with the level of FoxP3 expression in epitope-specific CD4 T cells Our study demonstrates that the biophysical properties of the epitope may dictate the functional properties of the CD4 T cell response. Understanding how epitope structure influences T cell function will provide new insight into viral pathogenesis and may improve vaccine design.