Increased frequency of ILT2-expressing CD56(dim)CD16(+) NK cells correlates with disease severity of pulmonary tuberculosis

Abstract

The functional role of ILT2 in anti-tuberculosis immunity remains to be elucidated. In this study, we investigated expression and functions of ILT2 on NK cells during TB infection. The frequency of CD56(dim)CD16(+) NK cells that expressed ILT2 was significantly elevated in patients with active pulmonary TB as compared with tuberculin-positive healthy controls (p < 0.0001). TB patients with Mycobacterium tuberculosis smear/culture-positive result had significantly higher frequency of ILT2-expressing CD56(dim)CD16(+) NK cells than those with M. tuberculosis smear/culture-negative result (p < 0.0001), suggesting that ILT2 expression on CD56(dim)CD16(+) NK cells correlated with disease severity of pulmonary TB. ILT2-expressing CD56(dim) NK cells had a functional defect, as evidenced by reduced expression of CD107a and IFN-γ. Spontaneous apoptosis in ILT2(+)CD56(dim) NK cells was higher than in ILT2(-) cells. Blocking of ILT2 signaling resulted in increased expression of CD107a on CD56(dim)CD16(+) NK cells. It is concluded that ILT2 has an inhibitory role on NK cells in patients with active TB.

Keywords: ILT2; Immunity; NK cells; Tuberculosis.