Type I IFN signaling restricts small intestinal virus-specific CD4 T cell accumulation and CD4 T cells are dispensable for barrier dysfunction during LCMV Cl13 infection. Related to Fig. 4. C57BL/6 mice were infected with LCMV Cl13 and treated with isotype (IgG1) or anti-IFNAR-1 Ab (αIFNAR; A–E) or anti-CD4 (αCD4) or isotype Ab (IgG2a) i.p. on days −2, −1, 0, and 5 p.i. (F and G) and analyzed on day 9 p.i. (A–F) FACS analysis of the small intestinal IEL or LPL compartments was done on day 9 p.i. (A and B) Frequencies and numbers (A) and PD1 mean fluorescence intensity (MFI; B) of I-A^bGP_67–77⁺ CD4 T cells. (C–E) Cytokine production upon ex vivo PMA/ionomycin (C and D) or GP_67–77 peptide (E) stimulation of LPL cells. (F) In vivo intestinal permeability to FD4. (G) Numbers of I-A^bGP_67–77⁺ in indicated organs. (A–G) Averages ± SEM are shown. Data are pooled from two (A and B) or three (F and G) independent experimental repeats or representative of two independent experimental repeats (C–E) with n = 3–5 mice/group. Although a tendency was consistently observed in all independent experiments, statistical significance was reached in one out of two experiments in A (right) and E (left, white versus pink squares). Statistical significance between Cl13 + IgG2a and Cl13 + αCD4 was only reached in one out of three experiments (F). *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001; two-tailed t test (A–C), Mann–Whitney test (G), and Kruskal–Wallis test with Dunn’s multiple comparisons’ correction (E–G).