CD4 T cells producing IFN-gamma in the lungs of mice challenged with mycobacteria express a CD27-negative phenotype

Protection against tuberculosis depends upon the generation of CD4(+) T cell effectors capable of producing IFN-gamma and stimulating macrophage antimycobacterial function. Effector CD4(+) T cells are known to express CD44(hi)CD62L(lo) surface phenotype. In this paper we demonstrate that a population of CD44(hi)CD62L(lo) CD4(+) effectors generated in response to Mycobacterium bovis BCG or M. tuberculosis infection in C57BL/6 mice is heterogeneous and consists of CD27(hi) and CD27(lo) T cell subsets. These subsets exhibit a similar degree of in vivo proliferation, but differ by the capacity for IFN-gamma production. Ex vivo isolated CD27(lo) T cells express higher amounts of IFN-gamma RNA and contain higher frequencies of IFN-gamma producers compared to CD27(hi) subset, as shown by real-time PCR, intracellular staining for IFN-gamma and ELISPOT assays. In addition, CD27(lo) CD4(+) T cells uniformly express CD44(hi)CD62L(lo) phenotype. We propose that CD27(lo) CD44(hi)CD62L(lo) CD4(+) T cells represent highly differentiated effector cells with a high capacity for IFN-gamma secretion and antimycobacterial protection at the site of infection.