Regulatory T cells dynamically control the primary immune response to foreign antigen

The population dynamics that enable a small number of regulatory T (T-R) 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 T-R 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 T-R Cell pool. Transfer of a polyclonal T-R cell population before immunization antagonized both polyclonal and TCR transgenic responses, whereas blocking T-R cell function enhanced those responses. These results define an inverse quantitative relationship between T-R and conventional T cells that controls the magnitude of the primary immune response. The high frequency of dividing T-R cells suggests degenerate TCR specificity enabling activation by a broad spectrum of Ags.