The preferential inhibition of memory T cells is observed under physiological conditions. (A) Physiologic numbers of responding endogenous polyclonal T cells preferentially inhibit memory T-cell proliferation. Naive (10⁶; top panels) or memory (2 × 10⁶; bottom panels) CD45.1 CFSE-labeled Marilyn cells were injected intravenously into B6 (i-vi) or OT-II (vii,viii) mice immunized by injection of 10⁶ H-Y peptide–loaded LPS-matured DCs into the footpad. (i,ii) Low initial frequencies of endogenous responding T cells do not inhibit naive or memory Marilyn T cells; naive or memory CD45.1 Marilyn T cells were injected on the same day as the H-Y peptide–loaded DCs. (iii-vi) Higher frequencies occurring later in the response inhibit proliferation of newly entering cells. Six days after the initiation of the primary endogenous response by injection of peptide-pulsed DCs into naive B6 hosts (iii,iv), or after a boost of mice that had been immunized 30 days previously (v,vi), new naive or memory CD45.1 CFSE-labeled Marilyn cells were injected, and proliferation was analyzed 6 days later. (vii,viii) Extremely low initial frequencies do not expand to inhibitory numbers in 6 days. Marilyn T cells were injected and analyzed as in panels iii,iv, but into OT-II hosts. Plots are of gated TCR⁺CD45.1⁺ cells from the DLN, and are representative of at least 2 experiments with at least 2 mice each per group. (B) Small numbers of responding T cells strongly inhibit small numbers of memory T cells. Five thousand naive (top panels) or memory (bottom panels) CD45.1 Marilyn T cells were injected into primed B6 hosts in the absence (left panels) or the presence (right panels) of a previous cohort of 5000 CD45.2 Marilyn T cells injected 6 days earlier, as in Figure 1A. Pooled draining lymph nodes of 8 to 20 mice were studied. Dot plots of gated TCR⁺CD45.1⁺ cells with the percentage of undivided cells are shown. (C) An immune response to endogenous DCs that have processed Ag from a peripheral solid tumor preferentially inhibits memory T-cell proliferation. CD45.2 B6 mice received a transplant of an MCA101 tumor cell line, transfected with the DBY protein.²⁴  Two days later, they were given a first cohort of CD45.2⁺ Marilyn T cells (right panels) or not (left panels). Naive (top panels) or memory (bottom panels) CD45.1⁺ Marilyn T cells were injected 5 days later. Dot plots of gated TCR⁺CD45.1⁺ cells from the immunization DLN are representative of at least 3 experiments with 2 mice each per group.