Expansion of Pathogen-Specific Mono- and Multifunctional Th1 and Th17 Cells in Multi-Focal Tuberculous Lymphadenitis

Abstract

BackgroundTh1 and Th17 responses are known to play an important role in immunity to pulmonary tuberculosis (PTB), although little is known about their role in extrapulmonary forms of tuberculosis (TB).MethodsTo identify the role of Th1, Th17, and Th22 cells in multi-focal TB lymphadenitis (TBL), we examined mycobacteria–specific immune responses in the whole blood of individuals with PTB (n = 20) and compared them with those with TBL (n = 25).ResultsElevated frequencies of CD4+ T cells expressing IFN- γ, TNF-α, and IL-2 were present in individuals with TBL compared with those with PTB at baseline and in response to ESAT-6 and CFP-10. Similarly, increased frequencies of CD4+ T cells expressing IL-17A, IL-17F, and IFN-γ were also present in individuals with TBL at baseline and following ESAT-6 and CFP-10 stimulation although no significant difference in frequency of Th22 cells was observed. Finally, frequencies of Th1 (but not Th17) cells exhibited a significantly negative correlation with natural regulatory T cell frequencies at baseline.ConclusionsMulti-focal TB lymphadenitis is therefore characterized by elevated frequencies of Th1 and Th17 cells, indicating that Th1 and Th17 responses in TB disease are probably correlates of disease severity rather than of protective immunity.

Altered CD8+ T cell frequency and function in tuberculous lymphadenitis

“…Therefore, an exaggerated Type 17 response, similar to the Type 1 response, occurs in active TBL individuals. This study also confirms that the response of CD8 + T cells in TBL is very similar to that of CD4 + T cells that we reported previously [12]. Whether these findings are the result of lymphoid tissue priming occurring more efficiently in TBL or whether it is the consequence of some intrinsic difference between the two disease states needs to be explored further.…”

“…We have previously shown that TBL is characterized by an antigen - specific expansion of CD4 + Th1 and Th17 cells [12]. Since TBL is felt to reflect a hematogenous disseminated form of TB, we postulated that CD8 + T cells might also play a different role in TBL compared to PTB.…”

Clinico-pathological features of tuberculosis due to mycobacterium tuberculosis Uganda genotype in patients with tuberculous lymphadenitis: a cross sectional study

“…Lymphadenopathy (superficial as well as systemic, including abdominal lymphadenopathy) is regarded as a manifestation of EPTB, where the mode of infection includes haematogenous spread from a primary focus or in miliary TB, lymphatic spread from infected lymph nodes, ingestion of bacilli and direct spread from adjacent viscera [35]. There are indications that the homeostatic immune response in tuberculous lymphadenitis is fundamentally different from that of pulmonary TB [36].…”

Tuberculous Lymphadenitis Is Associated with Enhanced Baseline and Antigen-Specific Induction of Type 1 and Type 17 Cytokines and Reduced Interleukin-1β (IL-1β) and IL-18 at the Site of Infection

“…Phorbol 12-myristate 13-acetate (PMA)-ionomycin (PMA-Iono; Calbiochem) was used as a positive-control stimulus at final concentrations of 12.5 ng/ml and 125 ng/ml. Dose-response studies have been performed previously, and the optimal concentrations were derived from the previous studies (4,5).…”

“…Previous studies have shown that TBL is characterized by a mycobacterial antigen-specific expansion of mono-and multifunctional Th1 and Th17 cells, as well as increased frequencies of CD8 ϩ T cells expressing type 1 and type 17 cytokines in comparison to those in individuals with PTB (4,5). In contrast, TBL is associated with reduced systemic and antigen-stimulated production of certain proinflammatory cytokines, including interleukin-1␤ (IL-1␤) and IL-18 (6), and elevated systemic levels of others, including IL-8 and tumor necrosis factor beta (TNF-␤) (7).…”