IL-1  Strikingly Enhances Antigen-Driven CD4 and CD8 T-Cell Responses

Protective immune response requires massive expansion of antigen-triggered naïve cells, extensive differentiation into effector cells, migration of effectors into the periphery, and generation of a functional memory compartment. IL-1β strikingly enhances expansion of antigen-primed CD8 and CD4 T cells in vivo. Its T-cell expansion in lymph nodes and spleen was direct, requiring that the stimulated T cells express IL-1R1. Immunization in the presence of IL-1β increases the frequency of IL-17- and IFN-γ-producing cells among primed CD4 cells and the frequency of granzyme B-expressing and IFN-γ-producing cells and of cytotoxic cells among primed CD8 cells. IL-1β-induced increase in the number of the activated CD4 and CD8 cells and augmented differentiation of the antigen-triggered T cells is very pronounced in liver and lungs. CD4 and CD8 cells primed in the presence of IL-1β display augmented cell number and enhanced cytokine production when rechallenged 2 mo after priming with antigen and lipopolysaccharide (LPS). In five in vivo models, IL-1β enhanced the protective value of weak vaccines. Preliminary analysis of in vivo gene expression in CD4 cells stimulated with IL-1β revealed that IL-1β caused gene expression changes consistent with the up-regulation of pathways involved in cell replication, cell survival, and enhanced energy metabolism. Thus, IL-1β enhances antigen-primed CD4 and CD8 T-cell expansion, differentiation, and migration to the periphery and memory, the specific functions required for generation of effective protective immune responses.