Antigen-Specific CD8+ T Cells and the Development of Central Memory during Mycobacterium tuberculosis Infection

Abstract

Whether true memory T cells develop in the face of chronic infection such as tuberculosis remains controversial. To address this question, we studied CD8+ T cells specific for the Mycobacterium tuberculosis ESAT6-related Ags TB10.3 and TB10.4. The shared epitope TB10.3/10.420–28 is presented by H-2 Kd, and 20–30% of the CD8+ T cells in the lungs of chronically infected mice are specific for this Ag following respiratory infection with M. tuberculosis. These TB10.3/10.420–28-specific CD8+ T cells produce IFN-γ and TNF and express CD107 on their cell surface, which indicates their likely role as CTL in vivo. Nearly all of the Ag-specific CD8+ T cells in the lungs of chronically infected mice had a T effector cell phenotype based on their low expression of CD62L and CD45RB. In contrast, a population of TB10.3/10.420–28-specific CD8+ T cells was identified in the lymphoid organs that express high levels of CD62L and CD45RB. Antibiotic treatment to resolve the infection led to a contraction of the Ag-specific CD8+ T cell population and was accompanied by an increase in the proportion of CD8+ T cells with a central memory phenotype. Finally, challenge of memory-immune mice with M. tuberculosis was accompanied by significant expansion of TB10.3/10.420–28-specific CD8+ T cells, which suggests that these cells are in fact functional memory T cells.

Poor correlation between BCG vaccination-induced T cell responses and protection against tuberculosis

“…Rapid accumulation of specific IFN-␥-secreting CD8 ϩ T cells is in line with previous observations of accelerated accumulation of CD8 ϩ T cells and early IFN-␥ production in tissues of vaccinated or infected and cured mice (13)(14)(15)18). At later time points after challenge, nonvaccinated mice showed similar numbers of specific IFN-␥ secreting CD8 ϩ T cells when compared with vaccinated mice.…”

“…After challenge infection, the secondary immune response in vaccinated mice or mice previously cured of M. tuberculosis infection is characterized by accelerated accumulation of effector T cells in infected tissues and early production of Th1 cytokines (12)(13)(14)(15)(16)(17)(18). Consequently, mycobacterial growth is restricted more efficiently in the initial phase of infection, and growth reaches a plateau at a 10-fold-lower level as compared with nonvaccinated animals.…”

CD4 + T-cell–independent mechanisms suppress reactivation of latent tuberculosis in a macaque model of HIV coinfection

“…CD8 + T cells have an essential but underappreciated role in the control of TB (12) and are critical for both natural and vaccine-induced immunity in nonhuman primates (NHPs) (13,14). In contrast, the role of B cells in immunity to TB is less well understood, although it appears they are required for the development of optimal immune responses to Mtb via various regulatory mechanisms (15)(16)(17).…”

Novel Vaccination Protocol with Two Live Mucosal Vectors Elicits Strong Cell-Mediated Immunity in the Vagina and Protects against Vaginal Virus Challenge

“…a lower proportion of IFN-␥-expressing cells (31.3% of Gagtetramer ϩ CD11a ϩ CD8 ϩ T cells were IFN-␥ ϩ ; data not shown). Some other studies of cytokine expression by Ag-specific CD8 ϩ T cells in peripheral mucosal tissues have also shown modest levels of expression (42,43).…”