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

Abstract

SUMMARY Protection against tuberculosis depends upon the generation of CD4+ T cell effectors capable of producing IFN-g 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-g production. Ex vivo isolated CD27 lo T cells express higher amounts of IFN-g RNA and contain higher frequencies of IFN-g producers compared to CD27 hi subset, as shown by real-time PCR, intracellular staining for IFNg 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-g secretion and antimycobacterial protection at the site of infection.

Influence of ESAT-6 Secretion System 1 (RD1) of Mycobacterium tuberculosis on the Interaction between Mycobacteria and the Host Immune System

“…Reduction in the expression of CD45RB is associated with effector phenotype in the T cell compartment. Accordingly, like M. tuberculosis H37Rv and in contrast to the parental BCG, BCG::RD1, with its intermediary degree of virulence, induced comparable influx of CD4 ϩ and CD8 ϩ T cells in the lungs with a characteristic activated CD44 high CD45RB Ϫ CD62L Ϫ cells as well as CD45RB Ϫ CD27 Ϫ T cells that may essentially constitute IFN-␥-producing T cells (20). BCG::RD1 aerosolization efficiently primed T cells specific for RD1-encoded immunogens.…”

“…It has been recently reported that Ag-experienced CD4 ϩ T cells accumulating within mycobacteria-infected lungs can be divided into CD27 ϩ or CD27 Ϫ subsets and that only the CD27 Ϫ subset constitutes highly differentiated IFN-␥-producing effector cells (20). Accordingly, we detected substantially increased percentages of CD45RB Ϫ CD27 Ϫ cells within both CD4 ϩ and CD8 ϩ T cell compartments of mice aerosol-infected with BCG::RD1 or H37Rv compared with those infected with control BCG (Fig.…”

CD27low CD4 T Lymphocytes That Accumulate in the Mouse Lungs during Mycobacterial Infection Differentiate from CD27high Precursors In Situ, Produce IFN-γ, and Protect the Host against Tuberculosis Infection

“…We have reported that CD62L low effector CD4 T lymphocytes that accumulate in the lungs during mycobacterial infection can be segregated into two subsets that express or lack CD27 on their surface (18). These subsets differ in their functional activity; the CD27 low CD4 T cells contain many more IFN-␥-producing cells and express higher levels of IFN-␥ mRNA at the single cell level than CD27 high cells.…”

“…Although CD27 is required for the successful generation of effector T lymphocytes, mature effector cells lose CD27. Loss of CD27 is a characteristic feature of both cytotoxic and IFN-␥-producing CD8 (24,25) and CD4 (18,26) T lymphocytes. What drives the down-regulation of CD27 and in which anatomical sites does this event take place remain unclear.…”

Targeting B-cell malignancies through human B-cell receptor specific CD4+T cells

“…46 However, recent studies found cytotoxic CD4 C T cells may represent a separate polarized functional subset of CD4 C T cells. 36,[47][48][49] The cytotoxic activity of the CD4 C T cells we identified was blocked by MHC class II antibody and CMA, indicating that the cytotoxic CD4 C T cells used the perforin pathway to kill tumors.…”