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. 2023 Mar 27;20(5):489–511. doi: 10.1038/s41423-023-00989-z

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© The Author(s) 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 4 — TFH and TR1 cell formation capacity in mice harboring IL-2-deficient T cells. A Cytokine secretion profiles of splenic CD4⁺ T cells from NOD.Cd4-Cre and NOD.Cd4-Cre.Il2^loxP/loxP mice upon stimulation with anti-CD3/anti-CD28 mAb-coated beads. The data correspond to 4–5 mice/strain from 2 experiments. B Reduction in the frequency of peripheral CD25⁺FOXP3⁺ CD4⁺ T cells in NOD.Cd4-Cre.Il2^loxP/loxP vs. NOD.Cd4-Cre mice. The data correspond to n = 5 mice/strain from 3 experiments. C NOD.Cd4-Cre.Il2^loxP/loxP mice had increased percentages of endogenous PD-1^hiCXCR5^hi cells in the spleen compared to NOD.Cd4-Cre mice. The data correspond to n = 5 mice/strain from 3 experiments. D Percentages of splenic PD-1^hiCXCR5^hi (TFH) and TACI⁺CD138⁺ (plasma) cells and anti-SRBC antibody titers in NOD.Cd4-Cre.Il2^loxP/loxP vs. NOD.Cd4-Cre mice upon SRBC immunization. The data correspond to n = 5 and 4 mice, respectively, from 2 experiments. E Anti-influenza virus IgG and IgM antibody titers (OD value) in 8–11-week-old male mice infected i.p. with 10⁷ EID₅₀ of the HKX31 (H3N2) strain twice at a 14-day interval. Fourteen days after the last infection, sera were collected and analyzed for the presence of H3N2-hemagglutinin (HA)-specific IgG and IgM via ELISA. The data correspond to n = 5, 3, 4, 3 and 3 mice from left to right. The data correspond to one experiment. F Average percentages of BDC2.5 mi/IA^g7 Tet⁺ CD4⁺ T cells in various lymphoid organs of BDC2.5 mi/IA^g7-NP-treated NOD.Cd4-Cre.Il2^loxP/loxP vs. NOD.Cd4-Cre mice. The data correspond to 5 mice/strain from 3 experiments. G Average percentages of PD-1^hiCXCR5^hi (TFH) cells within the Tet⁺ and Tet^– subsets of the mice in (F). H Cluster 2 (TR1):cluster 1 (TFH) ratios in the Tet⁺ subsets of BDC2.5 mi/IA^g7-NP-treated NOD.Cd4-Cre and NOD.Cd4-Cre.Il2^loxP/loxP mice, as measured via CyTOF. I Absolute numbers of cluster 1 (TFH) and cluster 2 (TR1) cells in the Tet⁺ subsets of BDC2.5 mi/IA^g7-NP-treated NOD.Cd4-Cre and NOD.Cd4-Cre.Il2^loxP/loxP mice, as measured via CyTOF. The data correspond to 5 mice/strain from 3 experiments. The data in all panels correspond to the mean ± SEM values. P values were calculated by the Mann‒Whitney U test