CD3 expression distinguishes two gamma delta T cell receptor subsets with different phenotype and effector function in tuberculous pleurisy

Tuberculous pleurisy is a naturally occurring site of Mycobacterium tuberculosis (Mtb) infection. Herein, we describe the expression of activation, natural killer (NK) and cell migration markers, as well as effector functions from gamma delta T cells in peripheral blood (PB) and pleural effusion (PE) from tuberculosis patients (TB). We observed a decreased percentage of circulating gamma delta T from TB patients and differential expression of NK as well as of chemokine receptors on PB and PE. Two subsets of gamma delta T cells were differentiated by the CD3/gamma delta T cell receptor (gamma delta TCR) complex. The gamma delta TCRlow subset had a higher CD3 to TCR ratio and was enriched in V delta(2+) cells, whereas most V delta(1+) cells belonged to the gamma delta TCRhigh subset. In PB from TB, most gamma delta TCRhigh were CD45RA(+)CCR7(-) and gamma delta TCRlow were CD45RA(+/-)CCR(7+)CXCR(3+). In the pleural space the proportion of CD45RA(-)CCR7(+)CXCR3(+) cells was higher. Neither spontaneous nor Mtb-induced interferon (IFN)-gamma production was observed in PB-gamma delta T cells from TB; however, PE-gamma delta T cells showed a strong response. Both PB- and PE-gamma delta T cells expressed surface CD107a upon stimulation with Mtb. Notably, PE-gamma delta TCRlow cells were the most potent effector cells. Thus, gamma delta T cells from PB would acquire a further activated phenotype within the site of Mtb infection and exert full effector functions. As gamma delta T cells produce IFN-gamma within the pleural space, they would be expected to play a beneficial role in tuberculous pleurisy by helping to maintain a T helper type 1 profile.