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CD3 expression distinguishes two gammadeltaT cell receptor subsets with different phenotype and effector function in
N Yokobori1, P Schierloh, L Geffner
1Departamento de Inmunología, Instituto de Investigaciones Hematológicas, Academia Nacional de Medicina, 1425 Buenos Aires, Argentina.
Insights
Tuberculous pleurisy involves Mycobacterium tuberculosis infection. Gamma delta T cells in pleural fluid show enhanced activation and effector functions, suggesting a beneficial role in fighting tuberculosis within the pleural space.
Area of Science:
- Immunology
- Infectious Diseases
- Cell Biology
Background:
- Tuberculous pleurisy is a common manifestation of Mycobacterium tuberculosis (Mtb) infection.
- Gamma delta T cells play a role in immune responses but their function in tuberculous pleurisy is not fully understood.
Purpose of the Study:
- To investigate the phenotype and effector functions of gamma delta T cells in peripheral blood and pleural effusion of tuberculosis patients.
- To determine the role of different gamma delta T cell subsets in the immune response to Mtb infection in the pleural space.
Main Methods:
- Flow cytometry was used to analyze the expression of activation, NK, and cell migration markers on gamma delta T cells.
- Interferon-gamma production and CD107a expression were measured upon stimulation with Mtb.
- Two subsets of gamma delta T cells, distinguished by their CD3/gammadeltaT cell receptor (gammadeltaTCR) complex, were characterized.
Main Results:
- A decreased percentage of circulating gamma delta T cells was observed in tuberculosis patients.
- Differential expression of NK and chemokine receptors was found on gamma delta T cells in peripheral blood and pleural effusion.
- Pleural effusion-derived gamma delta T cells exhibited a more activated phenotype and stronger interferon-gamma production compared to peripheral blood cells.
- The Vdelta2(+) enriched gammadeltaTCR(low) subset in pleural effusion demonstrated potent effector functions.
Conclusions:
- Gamma delta T cells migrate to the pleural space and acquire an activated phenotype during Mtb infection.
- Pleural effusion gamma delta T cells, particularly the gammadeltaTCR(low) subset, are potent effector cells contributing to the control of tuberculous pleurisy.
- These findings suggest that gamma delta T cells play a beneficial role in tuberculous pleurisy by promoting a T helper type 1 immune response.
Abstract:
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.
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