Regulatory T Cells Dynamically Control the Primary Immune Response to Foreign Antigen

Abstract

The population dynamics that enable a small number of regulatory T (TR) cells to control the immune responses to foreign Ags by the much larger conventional T cell subset were investigated. During the primary immune response, the expansion and contraction of conventional and TR cells occurred in synchrony. Importantly, the relative accumulation of TR cells at peak response significantly exceeded that of conventional T cells, reflecting extensive cell division within the TR cell pool. Transfer of a polyclonal TR cell population before immunization antagonized both polyclonal and TCR transgenic responses, whereas blocking TR cell function enhanced those responses. These results define an inverse quantitative relationship between TR and conventional T cells that controls the magnitude of the primary immune response. The high frequency of dividing TR cells suggests degenerate TCR specificity enabling activation by a broad spectrum of Ags.