Specific depletion of TFH and LCMV-specific CD4 T cells.

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Specific depletion of TFH and LCMV-specific CD4 T cells. Specific depletion of TFH and LCMV-specific CD4 T cells. (A) Experimental approach. Lethally irradiated CD4−/− mice were reconstituted with CD4-DTR (CD45.2+) BM and CD45.1+ B6 (control chimeras), CXCR5−/− (CXCR5−/− chimeras), or M25 (M25 chimeras) BM and persistently infected with 2 × 106 FFU LCMV clone 13. From d20 pi onward, continuous DTx treatment was initiated. (B) Longitudinal analysis of ratios of CD4-DTR–derived (CD45.2+) and CD45.1+ B6 (left), CXCR5−/− (CD45.1+; middle), or M25 (CD45.1+, right)-derived CD4 T cells in blood in untreated (upper) or DTx-treated (lower) mixed BM chimeras. (C) Ratios of CD4-DTR–derived (CD45.2+, white) and CD45.1+ B6 (black), CXCR5−/−(CD45.1+, red), or M25 (CD45.1+, blue)-derived CD4 T cells in the spleen (left) and mLN (right) on d70 pi in DTx-treated chimeras. (D) Total CD4 T cells in the spleen d70 pi of untreated or DTx-treated control (black), CXCR5−/− (red), or M25 (blue) chimeras. (E) Flow cytometric analysis of TFH cells (CXCR5+ PD-1+) in the spleen on d70 pi in untreated or DTx-treated control (black), CXCR5−/− (red) and M25 (blue) chimeras. (F) Number of gp61-tetramer+ CD4 T cells in untreated or DTx treated control (dark gray) or CXCR5−/− (red) chimeras at d100 pi in the spleen. (B, C, and F) One representative experiment of three is shown, n = 3 to 4 mice per group. Error bars represent means ± SD. (D and E) Pooled data of two independent experiments, n = 3 to 4 mice per group. Error bars represent means ± SEM. Statistical analysis was performed using Mann-Whitney U test, P > 0.05. Ute Greczmiel et al. Sci. Immunol. 2017;2:eaam8686 Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works