CD4 T cells are required for CoMtb-mediated protection from lesion necrosis. (A) Experimental outline. Subset of mice received CoMtb, then all mice aerosol infected with CD Mtb. Mice then received αCD4-depleting antibody or isotype from d-1 until harvest. n = 3–5 per group. (B) Representative confocal images showing presence of necrosis with αCD4 administration. Scale bar: 200 μm. (C) Pulmonary bacterial burdens. (D) Representative map showing 50 µm² neighborhoods, color-coded microenvironment, and heatmap showing cellular composition of clustered microenvironments. Scale bar: 1 mm. (E) Percent area of lesion comprised by each microenvironment. Uninvolved regions (gray) not included. (F) Percent of lesion comprised by necrotic region (pink). Single-group comparisons by Mann–Whitney U test. *P < 0.05, ***P < 0.001, ****P < 0.0001, and ns, P ≥ 0.05. Points represent individual mice. Data are representative of two independent experiments with at least four mice per group. See also Fig. S4.