Inversion of the V delta 1 to V delta 2 gamma delta T cell ratio in CVID is not restored by IVIg and is associated with immune activation and exhaustion

Author(s)

Paquin-Proulx, Dominic ; Barsotti, Nathalia Silveira ; Santos, Bianca A. N. ; Marinho, Ana Karolina B. B. ; Kokron, Cristina M. ; Carvalho, Karina I. ; Barros, Myrthes T. ; Kalil, Jorge ; Nixon, Douglas F. ; Kallas, Esper G.

• Document type: Journal article
• Source: MEDICINE; v. 95, n. 30 JUL 2016.
• Web of Science Citations: 3

Abstract

Common variable immunodeficiency (CVID) is defined by low levels of IgG and IgA, but perturbations in T cells are also commonly found. However, there is limited information on gamma delta T cells in CVID patients. Newly diagnosed CVID patients (n=15) were enrolled before and after intravenous IgG (IVIg) replacement therapy. Cryopreserved peripheral blood mononuclear cells were then used to study gamma delta T cells and CVID patients were compared to healthy controls (n=22). The frequency and absolute count of V delta 1 gamma delta T cells was found to be increased in CVID (median 0.60% vs 2.64%, P<0.01 and 7.5 vs 39, P<0.01 respectively), while they were decreased for V delta 2 gamma delta T cells (median, 2.36% vs 0.74%, P<0.01 and 37.8 vs 13.9, P<0.01 respectively) resulting in an inversion of the V delta 1 to V delta 2 ratio (0.24 vs 1.4, P<0.001). Markers of immune activation were elevated on all subsets of gamma delta T cells, and HLA-DR expression was associated with an expansion of V delta 1 gamma delta T cells (r=0.73, P=0.003). Elevated PD-1 expression was found only on V delta 2 gamma delta T cells (median 1.15% vs 3.08%, P<0.001) and was associated with the decrease of V delta 2 gamma delta T cells (r=-0.67, P=0.007). IVIg had no effect on the frequency of V delta 1 and V delta 2 gamma delta T cells or HLA-DR expression, but alleviated CD38 expression on V delta 1 gamma delta T cells (median MFI 965 vs 736, P<0.05). These findings suggest that immunological perturbations of gamma delta T cells are a general feature associated with CVID and are only partially reversed by IVIg therapy. (AU)

• FAPESP's process: 04/15856-9 - Prospective analysis of the virological and immunological characteristics in individuals with recent HIV-1 infection in the cities of São Paulo and Santos
• Grantee: Ricardo Sobhie Diaz
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 10/05845-0 - Cellular immune responses in infectious diseases and primary immunodeficiencies
• Grantee: Esper Georges Kallás
• Support Opportunities: Research Grants - Visiting Researcher Grant - International