Different phenotypes of CD8+ T cells associated with bacterial load in active tuberculosis

Abstract

Tuberculosis is an infectious disease that affects millions of people worldwide with an annual mortality rate of 1.3 million. The mechanisms contributing to the loss of balance of immune responses and progression to active tuberculosis disease are unknown. Although CD4+ and CD8+ T cells and the cytokines they produce are crucial for protection against tuberculosis they have different roles in tuberculosis immunology. The function of CD4+ T cells has been extensively studied; however, less is known about the phenotype and function of CD8+ T cells. This study evaluated the specific expression of IFN-γ, IL-17, IL-10, and TGF-β and ex vivo expression of perforin and granzyme-B by CD8+ T cells from active tuberculosis individuals compared with latent infected individuals and non-latent infected individuals. Tuberculosis responses were correlated with the baciloscopy score. We observed that the presence of IL-10 and TGF-β expression and down-expression of granzyme-B in CD8+ T cells correlated with increased sputum bacillary load in active tuberculosis individuals. These findings provide new insights into the role of CD8+ T cells in Mycobacterium tuberculosis disease.

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

“…In addition, the presence of CD3 − cells producing granzyme lends credibility to the role of NK cells in mediating control of both SIV and Mtb infection (37,38). The effector role of CD8 + T cells in the control of Mtb infection in humans has recently been described to inversely correlate with bacterial load in sputum (39), and HIV coinfection can impair Mtb-specific CD8 + T degranulation and proliferation (40). Thus, the effector roles of CD8 + T cells in curtailing reactivation need to be further investigated.…”

Increased intra- and extracellular granzyme expression in patients with tuberculosis

“…That would support the idea that the stimulation of CD8 þ T cells to produce more gzmA and B depends on the development of active disease. However, contradictory results were recently published, showing down-regulated expression of gzmB in CD8 þ T cells from active TB patients compared to latent TB and healthy controls [26].…”

CD8 T cells and Mycobacterium tuberculosis infection

“…CD8 T cells can also make a variety of cytokines, including IFN-γ, IL-17, TNF, IL-10, IL-2 and TGF-β, and these have been reported in human studies with TB patients(26). The production of IFN-γ by CD8 T cells is thought to be an important mediator of protection, however little work has been done to demonstrate the importance of the other cytokines produced by CD8 T cells in protection against M. tuberculosis .…”

“…Granzymes are expressed in cytotoxic T cells as well as NK and NKT cells. Granyzme B is expressed in peripheral blood CD8 T cells from M. tuberculosis infected humans, with higher expression seen in those with latent infection compared to active TUBERCULOSIS (26). Granzyme A expressing T cells were observed in human granulomas (27).…”