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

YOKOBORI N; SCHIERLOH P; GEFFNER L; BALBOA L; ROMERO M; MUSELLA R; CASTAGNINO J; DE STEFANO G; ALEMÁN M; DE LA BARRERA S; ABBATE E; SASIAIN MC

CLINICAL AND EXPERIMENTAL IMMUNOLOGY

British Society for Immunolgy. Blackwell Publishing Ltd

Año: 2009 vol. 157 p. 385 - 394

0009-9104

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 gammadeltaT cells in peripheral blood (PB) and pleural effusion (PE) from tuberculosis patients (TB). We observed a decreased percentage of circulating gammadeltaT from TB patients and differential expression of NK as well as of chemokine receptors on PB and PE. Two subsets of gammadeltaT cells were differentiated by the CD3/gammadeltaT cell receptor (gammadeltaTCR) complex. The gammadeltaTCR(low) subset had a higher CD3 to TCR ratio and was enriched in Vdelta2(+) cells, whereas most Vdelta1(+) cells belonged to the gammadeltaTCR(high) subset. In PB from TB, most gammadeltaTCR(high) were CD45RA(+)CCR7(-) and gammadeltaTCR(low) were CD45RA(+/-)CCR7(+)CXCR3(+). 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-gammadeltaT cells from TB; however, PE-gammadeltaT cells showed a strong response. Both PB- and PE-gammadelta T cells expressed surface CD107a upon stimulation with Mtb. Notably, PE-gammadeltaTCR(low) cells were the most potent effector cells. Thus, gammadeltaT cells from PB would acquire a further activated phenotype within the site of Mtb infection and exert full effector functions. As gammadeltaT 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.