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Published on: June 22, 2016
Altered CD8(+) T cell frequency and function in tuberculous lymphadenitis
Nathella Pavan Kumar1, Rathinam Sridhar2, Luke Elizabeth Hanna3
1National Institutes of Health-International Center for Excellence in Research, Chennai, India; National Institute for Research in Tuberculosis, Chennai, India.
CD8(+) T cells secreting Type1 and Type 17 cytokines and cytotoxic molecules play a major role in immunity and protection against pulmonary tuberculosis (PTB), although their role in tuberculous lymphadenitis (TBL) is not well known. To identify the distribution and function of CD8(+) T cells expressing Type1, Type 2 and Type 17 cytokines and cytotoxic molecules in TBL, we examined baseline and mycobacterial-antigen specific immune responses in the whole blood of individuals with PTB and compared them with TBL. TBL is characterized by elevated frequencies of baseline and mycobacterial-antigen stimulated CD8(+) T cells expressing Type 1 (IL-2 and TNFα) and Type 17 (IL-17A and IL-17F) cytokines in comparison to PTB individuals. In contrast, TBL individuals exhibited diminished frequency of CD8(+) T cells expressing perforin, granzyme B and CD107a. The blockade of IL-1R and IL-6R during antigenic stimulation resulted in significantly diminished frequencies of CD8(+) T cells expressing Type 1 and Type 17 cytokines in TBL. Therefore, our data suggest that TBL is characterized by an IL-1 and IL-6 dependent expansion of CD8(+) T cells expressing Type 1 and Type 17 cytokines as well as altered frequencies of cytotoxic molecules, reflecting an important association of these cells with the pathogenesis of TBL.
CD8(+) T cells secreting Type1 and Type 17 cytokines and cytotoxic molecules play a major role in immunity and protection against pulmonary tuberculosis (PTB), although their role in tuberculous lymphadenitis (TBL) is not well known. To identify the distribution and function of CD8(+) T cells expressing Type1, Type 2 and Type 17 cytokines and cytotoxic molecules in TBL, we examined baseline and mycobacterial-antigen specific immune responses in the whole blood of individuals with PTB and compared them with TBL. TBL is characterized by elevated frequencies of baseline and mycobacterial-antigen stimulated CD8(+) T cells expressing Type 1 (IL-2 and TNFα) and Type 17 (IL-17A and IL-17F) cytokines in comparison to PTB individuals. In contrast, TBL individuals exhibited diminished frequency of CD8(+) T cells expressing perforin, granzyme B and CD107a. The blockade of IL-1R and IL-6R during antigenic stimulation resulted in significantly diminished frequencies of CD8(+) T cells expressing Type 1 and Type 17 cytokines in TBL. Therefore, our data suggest that TBL is characterized by an IL-1 and IL-6 dependent expansion of CD8(+) T cells expressing Type 1 and Type 17 cytokines as well as altered frequencies of cytotoxic molecules, reflecting an important association of these cells with the pathogenesis of TBL.
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