Increased specific T cell cytokine responses in patients with active pulmonary tuberculosis from Central Africa

An understanding of T cell responses that are crucial for control of Mycobacterium tuberculosis (MTB) has major implications for the development of immune-based interventions. We studied the frequency of purified protein derivative (PPD)-specific CD3+ cells expressing interleukin-2 (IL)-2, gamma interferon (IFN)-γ, tumor necrosis factor (TNF)-α and IL-10 in HIV-negative pulmonary tuberculosis patients (TB, n = 30) as well as in healthy individuals (controls, n = 21) from Central Africa. Increased frequencies of PPD-stimulated CD3+ cells expressing IL-2, IFN-γ, and TNF-α in TB were seen when compared with frequencies of controls. The presence of type 1 cytokine biased responses in TB patients was supported by a shift in the distribution pattern of cytokine expression from exclusively IL-2 or TNF-α expression seen in controls towards an increased frequency of IFN-γ/IL-2 or IFN-γ/TNF-α co-expression in TB. Higher levels of PPD-induced IFN-γ in the supernatants from TB patients than from controls were found, which correlated with its intracellular expression. PPD was a weak inducer of IL-10 in T cells and insufficient in promoting cytokine production in TCRγδ+CD3+ cells. Non-specific stimulation with PMA and ionomycin revealed increased frequencies of CD4+ cells expressing IFN-γ in controls, while expression of IL-2, IL-4, IL-10, IL-13, and TNF-α was not different. Non-specific cytokine responses of TCRγδ+CD3+ cells were similar in all groups. Pulmonary TB in Central Africa is associated with enhanced expression and secretion of specifically induced cytokines that are frequently implicated in host defense against MTB.