Aberrant expression of receptors for the Fc portion of IgG (CD32) by T cells during pediatric RSV infection

SANANEZ I; SEERY V; ARRUVITO L; HOLGADO P; GEFFNER J; RAIDEN S; DE LILLO L

Tucuman

Congreso; Reunión Anual SAI 2019; 2019

SAI

Background: Respiratory syncytial virus (RSV) infection is the leading cause of hospitalization in infants. Antibodies can influence the outcome of disease through their interaction with the receptor for the Fc portion of IgG (CD32) expressed on target cells. The expression and function of CD32 in T cells from RSV-children has not been analyzed. Aims:1. To determine the expression, phenotype and the ratio between activating/inhibitory CD32 isoforms in CD4+ and CD8+ T cells. 2. To analyze the ability of RSV-specific IgG1 to mediate ADE of T cell infection. 3. To determine whether ligation of CD32 affects the functional profile of CD4+ T cells and/or enhances CD8+ T cell cytotoxicity. MethodsWe used PBMCs from hospitalized RSV-children (n=98) and healthy donors (n=46, HD) to evaluate:1. CD32 expression/phenotype by flow cytometry and RT-qPCR.2. Antibody-enhancement of RSV-infection in T cells by flow citometry.3. Cytokines secreted by CD4+ T cells by multiplex assays and CD8+ cytotoxicity after CD32-stimulation.ResultsA higher frequency of CD32 in T cells that correlated with activation markers was observed in RSV-children compared to HD, with a predominance of the activating isoform (CD32a). RSV complexed with specific antibodies did not enhance the infection of T cells. Finally, the stimulation through CD32 promoted not only the secretion of IL2, IFN-g TNF-a, IL-4, IL-6, IL-10 and IL8 by CD4 + T cells but also the function of CD8+ T cells from RSV-children.ConclusionsOur observations identify an unanticipated role for IgG in modulating T cells during RSV infection. The characterization of this mechanism may improve therapeutic strategies.