Phenotypic and functional analyses on T-cell subsets in lymph nodes of MRL/Mp-lpr/lpr mice.

By means of killing and/or FACS sorting the double-negative (DN) Lyt2-, L3T4- cells, Lyt2+ or L3T4+ cells and B220- cell populations were separated from T-cell-enriched lymph node (LN) cells of 4- to 5-month-old MRL/Mp-lpr/lpr mice. These highly purified cell populations were examined for their proliferative responses, interleukin 2 (IL2) production and expression of IL2 receptor (IL2R) in response to phorbol myristate acetate (PMA) and the calcium ionophore A23187 (A2) or PMA plus concanavalin A. The DNT-cell population was unable to respond to the stimuli and did not express IL2R. Thus the DN T cells, the major population responsible for the lymphadenopathy, possess fundamental defects in signal transduction as well as in the IL2-IL2R-mediated function. On the other hand, Lyt2+ or L3T4+ T cells obtained by sorting or B220- cells purified by the sorting after killing B220+ cells, exhibited proliferative responses indistinguishable from that of LN cells of the congenic MRL/Mp-+/+(+/+) mice. These cells also expressed IL2R after stimulation, however, the amount of IL2 produced was significantly lower than that produced by congenic +/+ cells. This suggested that phenotypically normal Lyt2+ or L3T4+ T cells of lpr LNs also possess a partial defect in the signal transduction system for IL2 production under the influence of the lpr gene.