Quantitative studies on T-cell functions in MRL/MP-Lpr/Lpr mice. I. Frequency analysis of precursor cells of proliferating, cytotoxic, and T-cell growth factor-secreting T lymphocytes reveals an increase in absolute numbers, with a concomitant decrease in percentage of immunocompetent cells.

A limiting dilution system has been applied to compare precursor frequencies of proliferating T lymphocytes (PTL-P), of T-cell growth factor-secreting T cells (TTCGF-P), and of cytotoxic T cells (CTL-P) in lymphocyte populations of aged, MRL/MP-lpr/lpr (MRL-lpr) mice and the congeneic strain MRL/MP- +/+ (MRL-n,), or the H-2k-compatible strains AKR/N and B10.BR responding to the mitogen concanavalin (ConA), to alloantigens (H-2) or to trinitrophenol (TNP)-modified syngeneic cells. In lymph node and spleen populations of 3- to 8-month-old MRL-lpr mice, the frequencies of H-2d- or ConA-reactive PTL-P and TTCGF-P, and of CTL-P sensitive to either H-2d, TNP, or ConA stimuli were between 5 to 30 times lower than in the corresponding populations of the other three strains. Furthermore, the frequencies of CTL-P progressively decreased in MRL-lpr mice from 3 to 8 months of age. In contrast, the absolute numbers of immunologically competent precursor T cells (PTL-P, TTCGF-P, CTL-P) was in general approximately 2- to 5-fold higher in MRL-lpr than in the control mice. However, these normal T cells do not seem to expand proportionally with the progressive lymphadenopathy in MRL-lpr mice since the number of T lymphocytes recovered from lymph nodes of the individual animals tested exceeded those of tissues from control mice by 30- to 300-fold. The results therefore suggest that mature T cells are progressively diluted out by abnormal lymphocytes in lymphocyte populations of aging MRL-lpr mice, thus causing a decrease of immune responses in vitro and possibly also affecting optimal cellular interactions in vivo.