PMC

A–D Jinx mice were infected with 200 pfu LCMV‐WE i.v. Pooled data from ATCT experiments irrespective of the number and composition of the transferred cell population analyzed ≥ day 20 after therapy. (A) Frequency of “functional” transferred CD8 T cells (funct. trsf. CD8; KLRG1⁺ and/or CD127⁺) of all lymphocytes in the spleen was correlated with virus clearance to determine therapy success. Cured (LCMV‐free) recipients (gray bars) versus not cured (persistently infected) recipients (black bars; n = 99). (B) Procedure described in (A) was repeated for “functional” transferred CD8 T cells, which are PD‐1^lowLAG3^low (n = 92). (C, D) Jinx mice received on day 15 p.i. 1 × 10⁷ lymphocytes (Jinx + lym), 4 × 10⁶ purified CD3 (Jinx + CD3), or 4 × 10⁶ purified CD8 T cells (Jinx + CD8) from LCMV‐immune wild‐type mice. Alternatively, Jinx mice received effector T cells from acutely LCMV‐infected WT mice (day 5–15 p.i.; Jinx + eff). Frequency of transferred “functional” CD8 T cells (PD‐1^lowLAG3^low or CD127⁺ and/or KLRG1⁺) in recipient Jinx mice at the indicated time points after therapy in (C) spleen and (D) blood. Successful LCMV clearance from all organs (cured, open symbol) versus no LCMV clearance (not cured, filled symbol). (n (C) = 10 Jinx + eff. – day 20, 13 Jinx + CD3 – day 20, 15 Jinx + CD3 > day 100, 7 Jinx + lym. > day 100, 4 Jinx + CD8 > day 100). (n (D) = 5 Jinx + eff. – day 20–35, 7 Jinx + lym. – day 20–35, 5 Jinx + CD3 – day 20–35, 12 Jinx + CD3 > day 100, 3 Jinx + CD8 > day 100).
Data information: Horizontal lines in graphs represent mean values. Dotted lines (A–D) indicate thresholds. Data are mean ± SEM with n = 92–99 in 18 independent experiments (A, B) and n = 5–19 in 1–8 independent experiments (C, D). Statistics: Mann–Whitney test (C, D), ns P > 0.05.

Jinx mice and heterozygous littermates (WT) were infected with 200 pfu LCMV‐WE i.v. On day 15 p.i. 4 × 10⁶ CD3 T cells from LCMV‐immune WT mice were transferred to Jinx mice (Jinx + ATCT). As controls, Jinx and WT mice were left untreated. A further experimental group was re‐challenged with 10⁵–10⁶ pfu LCMV‐Armstrong intraperitoneally (Jinx + ATCT+challenge) more than 45 days after therapy. AMouse survival was followed for 22 weeks p.i. or postchallenge (n = 88 Jinx, 43 Jinx + ATCT, 7 Jinx + ATCT + challenge; n (survival until week 22 p.i./challenge) = 2/38 Jinx, 21/22 Jinx + ATCT, 7/7 Jinx + ATCT + challenge in ≥ 2 experiments).B, CBodyweight and virus titres in week 17 p.i. or postchallenge (n = 12 Jinx, 21 Jinx + ATCT, 7 Jinx + ATCT + challenge, 17 WT).DFrequency of transferred CD8 T cells in the spleens of recipients 1 day (n = 4), 3 weeks (n = 16) and 15 weeks (n = 21) after therapy or 15 weeks after challenge (n = 7).
Data information: Horizontal lines in graphs represent mean values. Horizontal dashed line (C) indicates the detection limit. Data are mean ± SEM with n = 7–21 in ≥ 2 experiments. Statistics: log‐rank test (A), Mann–Whitney test (B, D), ***P ≤ 0.001; ****P ≤ 0.0001.
Source data are available online for this figure.

Jinx mice (Jinx) and heterozygous littermates (WT) were infected with 200 pfu LCMV‐WE intravenously. On day 15 post infection (p.i.), mice remained untreated (Jinx, WT) or 4 × 10⁶ purified CD3 T cells from LCMV‐immune WT mice were transferred to Jinx mice (Jinx + ATCT). Transferred CD8 T cells (trsf.) were distinguished from endogenous CD8 T cells (endog.). A, BOn day 20 after therapy, endogenous and transferred CD8 T cells (column II), as well as LCMV‐GP_33–41‐specific CD8 T cells (column III), were analyzed by flow cytometry: frequency of TCF‐1⁺ or TOX⁺. The same analyses were performed more than 100 days after therapy (column IV).CSplenocytes were restimulated with LCMV‐GP_33–41. The frequencies of transferred WT CD8 T cells in Jinx recipients and WT CD8 T cells expressing IFNγ and TNFα or IFNγ and CD107a after restimulation were determined on day 20 or > 100 days after therapy start (C, columns II, IV).
Data information: Horizontal lines in graphs represent mean values. ns P > 0.05; *P ≤ 0.05; **P ≤ 0.01; ***P ≤ 0.001; ****P ≤ 0.0001. Data are mean ± SEM with n (A–C) 3–19 mice in 1–5 experiments. Statistics: unpaired t‐test (A column II, III, IV; B column IV), Mann–Whitney test (B column II, III; C column II, IV). Detailed information n: A. (II) n = 9 Jinx, 11 Jinx + ATCT (9× trsf. cells), 11 WT in 4 experiments; (III) n = 4 Jinx, 5 Jinx + ATCT (3× trsf. cells), 6 WT in 2 experiments; (IV) n = 10 Jinx + ATCT, 3 WT in 2 experiments. B. (II) n = 9 Jinx, 11 Jinx + ATCT (6× trsf. cells), 11 WT in 4 experiments; (III) n = 5 Jinx, 6 Jinx + ATCT (3× trsf. cells), 7 WT in 2 experiments; (IV) n = 9 Jinx + ATCT (6× trsf. cells), 3 WT in 2 experiments. C. (II) IFNγ/TNFα: n = 16 trsf. cells in Jinx + ATCT, 16 WT in 5 experiments; (II) IFNγ/CD107a: n = 11 trsf. cells in Jinx + ATCT, 10 WT in 3 experiments; (II) IFNγ/TNFα: n = 6 trsf. cells in Jinx + ATCT, 3 WT in 1 experiment; (IV) IFNγ/CD107a: n = 6 trsf. cells in Jinx + ATCT, 3 WT in 1 experiment.

Jinx mice and heterozygous littermates (WT) were infected with 200 pfu LCMV‐WE i.v. On day 15 p.i., 4 × 10⁶ purified CD3 T cells from LCMV‐immune WT mice were transferred to Jinx mice (Jinx + ATCT). Transferred CD8 T cells (trsf.) were distinguished from endogenous CD8 T cells (endog.). As controls, Jinx and WT mice were left untreated. A–COn day 35 p.i., endogenous and transferred CD8 T cells (columns I and II), as well as LCMV‐GP_33–41‐specific CD8 T cells (column III) in the spleen, were analyzed by flow cytometry: (A) frequency of KLRG1⁺ and/or CD127⁺, (B) PD‐1⁺/LAG3⁺ and (C) TCF‐1⁻/TIM3⁺ CD8 T cells (C) The same analyses were performed more than 100 days after therapy/115 days after infection (column IV).
Data information: FACS plots are representative of the respective mouse groups. Horizontal lines in graphs represent mean values. Data are mean ± SEM with n = 8–15 per group in 2–5 independent experiments. Detailed information n: A. (II) n = 12 Jinx, 15 Jinx + ATCT (15× trsf cells), 15 WT in 5 experiments; (III) n = 12 Jinx, 13 Jinx + ATCT (13× trsf cells), 15 WT in 5 experiments; (IV) n = 15 Jinx + ATCT (15× trsf cells), 8 WT in 3 experiments. B. (II) n = 14 Jinx, 15 Jinx + ATCT (13× trsf cells), 18 WT in 5 experiments; (III) n = 14 Jinx, 15 Jinx + ATCT (13× trsf cells), 18 WT in 3 experiments; (IV) n = 15 Jinx + ATCT (15× trsf cells), 8 WT in 3 experiments. C. (II) n = 9 Jinx, 11 Jinx + ATCT (9× trsf cells), 13 WT in 4 experiments; (III) n = 9 Jinx, 11 Jinx + ATCT (9× trsf cells), 13 WT in 4 experiments; (IV) n = 9 Jinx + ATCT (9× trsf cells), 5 WT in 2 experiments. Statistics: unpaired t‐test (A column IV, B column II, C column II and III), Mann–Whitney test (A column II, III, B column III and IV, C column IV), ns P > 0.05; *P ≤ 0.05; ****P ≤ 0.0001.