title: Clonal expansions of CD8+ T cells with IL-10 secreting capacity occur during chronic Mycobacterium tuberculosis infection.
abstract: The exact role of CD8(+) T cells during Mycobacterium tuberculosis (Mtb) infection has been heavily debated, yet it is generally accepted that CD8(+) T cells contribute to protection against Mtb. In this study, however, we show that the Mtb-susceptible CBA/J mouse strain accumulates large numbers of CD8(+) T cells in the lung as infection progresses, and that these cells display a dysfunctional and immunosuppressive phenotype (PD-1(+), Tim-3(+), CD122(+)). CD8(+) T cell expansions from the lungs of Mtb-infected CBA/J mice were also capable of secreting the immunosuppressive cytokine interleukin-10 (IL-10), although in vivo CD8(+) T cell depletion did not significantly alter Mtb burden. Further analysis revealed that pulmonary CD8(+) T cells from Mtb-infected CBA/J mice were clonally expanded, preferentially expressing T cell receptor (TcR) Vβ chain 8 (8.2, 8.3) or Vβ 14. Although Vβ8(+) CD8(+) T cells were responsible for the majority of IL-10 production, in vivo depletion of Vβ8(+) did not significantly change the outcome of Mtb infection, which we hypothesize was a consequence of their dual IL-10/IFN-γ secreting profiles. Our data demonstrate that IL-10-secreting CD8(+) T cells can arise during chronic Mtb infection, although the significance of this T cell population in tuberculosis pathogenesis remains unclear.
authors.affiliation: Department of Microbial Infection and Immunity, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Cyktor
authors.forename: Bridget
authors.initials: B
authors.lastname: Carruthers
authors.forename: Gillian L
authors.initials: GL
authors.lastname: Beamer
authors.forename: Joanne
authors.initials: J
authors.lastname: Turner
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D020022:Genetic Predisposition to Disease; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000378:metabolism*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D009169:Mycobacterium tuberculosis; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology*
chemical_list: D011948:Receptors, Antigen, T-Cell; D016753:Interleukin-10