Depletion of circulating regulatory T cells during severe respiratory syncytial virus infection in young children

RAIDEN S; PANDOLFI J; PAYASLIÁN F; ANDERSON M; RIVAROLA N; FERRERO FERNANDO; URTASUN M; FAINBOIM L; GEFFNER J; ARRUVITO L

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE

AMER THORACIC SOC

Año: 2014 vol. 18 p. 865 - 868

1073-449X

Our observations reveal a dramatic and prolonged reduction in the frequency of the two populations of peripheral blood FOXP3+CD4+ Tregs in severe RSV-infected infants. These results are consistent with previous observation showing lower levels of FOXP3 mRNA in whole blood from RSV-infected children compared with healthy children. Very little information is available about human Tregs in the course of acute viral infection. However, increased frequencies of Tregs during human infection by dengue and influenza A virus (H1N1) have been reported. In addition, observations made in murine models of RSV infection showed not only that depletion of Tregs resulted in enhanced disease, suggesting that Tregs suppress pathological immune responses, but also that infection induced the recruitment of Tregs in the lung and mediastinal lymph nodes. Taking these observations into account, we speculate that the depletion of circulating Tregs in RSV-infected infants could reflect a massive recruitment of Tregs from the bloodstream to the infected lungs or the lung draining lymph nodes. Alternatively, it could reflect a high susceptibility to apoptosis of infant Tregs during the course of RSV infection as well as the possibility that in the setting of inflammation associated to severe RSV infection some Tregs might become unstable losing FOXP3 expression and acquiring an effector-like phenotype. Further observations are needed to test these hypotheses.