Abstract
Tuberculous lymphadenitis (TBL) individuals exhibit reduced frequencies of CD8+ T cells expressing cytotoxic markers in peripheral blood. However, the frequencies of cytotoxic marker expressing CD4+, CD8+ T cells, and NK cells at the site of infection is not known. Therefore, we measured the baseline and mycobacterial antigen specific frequencies of cytotoxic markers expressing CD4+, CD8+ T cells, and NK cells in the LN (n = 18) and whole blood (n = 10) of TBL individuals. TBL LN is associated with lower frequencies of CD4+ T cells expressing cytotoxic markers (Granzyme B, CD107a) compared to peripheral blood at baseline and in response to PPD, ESAT-6, and CFP-10 antigen stimulation. Similarly, lower frequencies of CD8+ T cells expressing cytotoxic markers (Perforin, Granzyme B, and CD107a) were also present in the TBL LN at baseline and following (except perforin) antigen stimulation. Finally, at baseline and after antigen (PPD, ESAT-6, and CFP-10) stimulation, frequencies of NK cells expressing cytotoxic markers were also significantly lower in TBL LN compared to whole blood. Hence, TBL is characterized by diminished frequencies of cytotoxic marker expressing CD4+, CD8+ T cells, and NK cells at the site of infection, which might reflect the lack of protective immune responses at the site of Mycobacterium tuberculosis infection.
Highlights
Cytotoxic T lymphocytes (CTL) are mainly involved in the killing of macrophages (Mφ) infected cells with Mycobacterium tuberculosis (Mtb) [1, 2]
In the present study, we have examined the frequencies of CD4+ and CD8+ T cells and Natural killer (NK) cells expressing cytotoxic markers in the lymph nodes and compared them with peripheral blood of Tuberculous lymphadenitis (TBL) individuals
To determine the cytotoxic marker expressing CD4+ T cells in TBL individuals, we used multi-color flow cytometry to define the frequencies of baseline and mycobacterial antigen-specific stimulated CD4+ T cells expressing perforin (PFN), granzyme B (GZE B), and CD107a (Figure 1)
Summary
Cytotoxic T lymphocytes (CTL) are mainly involved in the killing of macrophages (Mφ) infected cells with Mycobacterium tuberculosis (Mtb) [1, 2]. Deficiencies in the production of both IFNγ and interleukin (IL)-12 highly elevate the risk of tuberculosis (TB) disease They are important for stimulating the antimicrobial action of macrophages [9, 10]. Like CD4, CD8+ T cells are significantly important in providing resistance to Mtb infection by activating various [IFNγ, tumor necrosis factor (TNFα), IL-2] cytokines and by eliminating Mtb infected macrophages [11,12,13]. They have the ability to induce cytolytic activity through granule (i.e., perforin, granzyme, and granulysin) production [14, 15]
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