CD4 Help Enhances Expansion of Myeloids and DCs

Abstract

CD4 T cell help has been known to induce DC "licensing" for an optimal CD8 T cell immune response during viral and pathogenic antigen immunization models. However, the exact role and mechanism for the DC licensing by CD4 help have not been fully identified. To define the role of CD4 T cell help, I tracked and compared the dynamics of myeloids and immature DCs during helped and helpless CD8 T cell responses to a cellular antigen, minor histocompatibility antigen H60. DC maturation and functionality was similar between helped and helpless responses. However, there was a quantitative increase in both myeloids and immature DC populations, in correlation with an increase in the number of mature DCs. I identified a myeloid population, MHCII+ and MHCII-CD11c-CD11b+Ly6ChiLy6Gint subsets, that were increased during the helped response. They had a phenotype similar to that of immature and mature DCs, suggesting a DC precursor population. The expansion of myeloids and DCs, and the DC precursor myeloid population during the helped response was also confirmed by comparison of the myeloid and DC cell kinetics during helped responses induced in B6 wild type and CD40-deficient mice. The same findings were observed in analysis of in vitro bone marrow cell culture kinetics. These data suggest that the role of CD4 help is not enhancement of DC maturation bona fide, but rather a quantitative increase of myeloid cells and DC precursors to subsequently increase mature DC population.