IN-VIVO CD4(-NODE T-CELLS FROM LPR MICE GENERATE CD4(-)CD8(-)B220(+)TCR-BETA(LOW) CELLS() LYMPH)

Double-negative CD4(-)CD8(-) T cells (DNT) have been shown to be the m ajor population of T cells responsible for the massive lymphadenopathy associated with the early onset of the lupus-like syndrome in mice be aring the lpr gene. Previously, we demonstrated that these cells do no t proliferate in the peripheral lymphoid organs that they invade; furt hermore, we showed that a wide range of CD4 Ag expression was observed on lymph node CD4(+) T cells. In this study, we used an in vivo trans fer system to analyze the progeny of CD4(+) T cells from B6-lpr/lpr mi ce. Purified CD4(+) T cells injected into B6 nude mice are able to gen erate DNT cells; furthermore, phenotypic and functional characterizati ons of the DNT cells generated in vivo show that they share the same p roperties as DNT cells from B6-lpr/lpr mice. We also show that, after in vitro bromodeoxyuridine incorporation, only CD4(+) cells cycle. Fro m these studies, we conclude that the lymphoproliferation occurs at th e CD4(+) stage and that downregulation of this Ag probably is followed by arrest of the cell cycle.