Extended Data Fig. 6: Immune checkpoint blockade promotes TCR7B8-mediated CNS inflammation.
From: Gut inflammation promotes microbiota-specific CD4 T cell-mediated neuroinflammation
(A-G) The transfer of naïve TCR7B8 CD4 T cells into Rag2−/− hosts with the i.p. injection of 300 μg of Anti-CTLA4 and Anti-PD-1 antibodies (ICB) or control antibodies. (A) Neurological Scores, (B) incidence of neurological disorders, and (C) body weight. (D) Representative FACS plots and (E) numbers of CD4 T cells (left), IFNγ/IL-17A DP CD4 T cells (middle), TNFα-producing CD4 T cells (right) in the brain. (F) Representative FACS plots and (G) numbers of CD4 T cells (left), IFNγ/IL-17A DP CD4 T cells (middle), TNFα-producing CD4 T cells (right) in the Spinal cord. The experiments were conducted twice, and the data were combined except for the body weight data shown in C. (H-I) The transfer of naïve TCR7B8 CD4 T cells into WT hosts with or without the i.p. injection of 300 μg of Anti-CTLA4 and Anti-PD-1 antibodies. (H) Neurological Scores and (I) Faecal LCN2 detection in freshly collected faecal pellets at 7 weeks after transfer. The experiments were conducted two to three times, and the data were combined. (J-K) The transfer of Cd45.2/Cd45.2 TCR7B8 CD4 naïve T cells into CD45.1/Cd45.1 WT and Rag2−/− hosts with or without the i.p. injection of 300 μg of Anti-CTLA4 and Anti-PD-1 antibodies or control antibody. Seven weeks following the transfer, donor and recipient CD4 T cells were analyzed. (J) Representative flow plots of IFNγ and IL-17A producing total CD4 + T cells (including donor- and host-derived CD4 T cells) (left). Frequencies of IFNγ-producing and IFNγ/IL-17A double-producing CD4 T cells in the indicated tissues with or without CPI treatment 7 weeks following the transfer (right). (K) Representative flow plots of TCR7B8 CD4 T cells as CD45.2 + TCRβ + CD4 + T cells in the spinal cord (left). Numbers of CD45.2 + TCR7B8 CD4 T cells were compared (right). Results are presented as the mean ± SEM, with dots representing individual mice. (A, C, H) Two-way ANOVA, (B) Mantel-Cox test (E, G, J, K) Student’s t-test, (I) One-way ANOVA.
