Dampening of IL-2 function in infants with severe respiratory syncytial virus disease

SANANEZ, INÉS; RAIDEN, SILVINA; ERRA DIAZ, FERNANDO; DE LILLO, LEONARDO; HOLGADO, MARÍA PÍA; GEFFNER, JORGE; ARRUVITO, LOURDES

JOURNAL OF INFECTIOUS DISEASES

UNIV CHICAGO PRESS

Año: 2018

0022-1899

Background: FOXP3+ regulatory T cells (Tregs) restraint the destructive potential of the immune system. We have previously reported a pronounced reduction of circulating Tregs in infants with severe respiratory syncytial virus (RSV) disease. Because IL-2 is critical for Treg growth, survival and activity, we here analyzed IL-2 production and function in RSV-infected infants.Methods: Phenotype, proliferation, IL-2 production and IL-2 signaling in CD4+ T cells were analyzed by flow cytometry. Serum CD25 levels were quantified by ELISA.Results: CD4+ T cells from RSV-infected infants produced lower amounts of IL-2 and showed a reduced proliferative response compared with healthy infants. IL-2 increased CD4+ T cell proliferation and FOXP3 expression in both, healthy and RSV-infected infants. However, despite IL-2 induced a similar pattern of STAT5 phosphorylation, the proliferative response of CD4+ T cells and the expression of FOXP3+ remained significantly lower in RSV-infected infants. Interestingly, we found a negative correlation between disease severity and both, the production of IL-2 by CD4+ T cells and the ability of exogenous IL-2 to restore the pool of FOXP3+CD4+ T cells.Conclusions: A reduced ability to produce IL-2 and a limited response to this cytokine might affect the function of CD4+ T cells in RSV-infected infants.Key words: Respiratory syncytial virus, infants, severe bronchiolitis, CD4+ T cells, FOXP3, IL-2, sCD25, CD25.