Abstract
BackgroundLymph node tuberculosis (LNTB) is the most frequent extrapulmonary form of tuberculosis (TB). Studies of human tuberculosis at sites of disease are limited. LNTB provides a unique opportunity to compare local in situ and peripheral blood immune response in active Mycobacterium tuberculosis (Mtb) disease. The present study analysed T regulatory cells (Treg) frequency and activation along with CD4+ T cell function in lymph nodes from LNTB patients.ResultsLymph node mononuclear cells (LNMC) were compared to autologous peripheral blood mononuclear cells (PBMC). LNMC were enriched for CD4+ T cells with a late differentiated effector memory phenotype. No differences were noted in the frequency and mutifunctional profile of memory CD4+ T cells specific for Mtb. The proportion of activated CD4+ and Tregs in LNMC was increased compared to PBMC. The correlation between Tregs and activated CD4+ T cells was stronger in LNMC than PBMC. Tregs in LNMC showed a strong positive correlation with Th1 cytokine production (IL2, IFNγ and TNFα) as well as MIP-1α after Mtb antigen stimulation. A subset of Tregs in LNMC co-expressed HLA-DR and CD38, markers of activation.ConclusionFurther research will determine the functional relationship between Treg and activated CD4+ T cells at lymph node sites of Mtb infection.
Highlights
Lymph node tuberculosis (LNTB) is the most frequent extrapulmonary form of tuberculosis (TB)
Memory subsets of CD4+ T cells were defined according to expression of CD45RA and CCR7 and only the effector subset was modestly increased in Lymph node mononuclear cells (LNMC) compared to peripheral blood mononuclear cells (PBMC) (p = 0.0002) (Fig. 1b)
T cell functional profiles in response to Mycobacterium tuberculosis (Mtb) antigens were compared between LNMC and PBMC
Summary
Lymph node tuberculosis (LNTB) is the most frequent extrapulmonary form of tuberculosis (TB). Studies of human tuberculosis at sites of disease are limited. LNTB provides a unique opportunity to compare local in situ and peripheral blood immune response in active Mycobacterium tuberculosis (Mtb) disease. The present study analysed T regulatory cells (Treg) frequency and activation along with CD4+ T cell function in lymph nodes from LNTB patients. Mycobacterium tuberculosis (Mtb) infection is a major global health problem with approximately 10.4 million cases and 1.4 million deaths from tuberculosis (TB) in 2015 [1]. Lymph node tuberculosis (LNTB) is the most frequent extrapulmonary form [1]. Cellular immune responses play a pivotal role in control of Mtb infection with CD4+ T cells having the central role. After infection CD4+ T cells undergo activation manifested by expression of surface molecules including
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