Immunological priming - either in the context of prior infection or vaccination - elicits protective responses against subsequent () infection. However, the changes that occur in the lung cellular milieu post-primary infection and their contributions to protection upon reinfection remain poorly understood. Here, using clinical and microbiological endpoints in a non-human primate reinfection model, we demonstrate that prior infection elicits a long-lasting protective response against subsequent exposure and that the depletion of CD4 T cells prior to rechallenge significantly abrogates this protection. Leveraging microbiologic, PET-CT, flow cytometric, and single-cell RNA-seq data from primary infection, reinfection, and reinfection-CD4 T cell depleted granulomas, we identify differential cellular and microbial features of control. The data collectively demonstrate that the presence of CD4 T cells in the setting of reinfection results in a reduced inflammatory lung milieu characterized by reprogrammed CD8 T cell activity, reduced neutrophilia, and blunted type-1 immune signaling among myeloid cells, mitigating disease severity. These results open avenues for developing vaccines and therapeutics that not only target CD4 and CD8 T cells, but also modulate innate immune cells to limit disease.