T cell activation in patients with severe hantavirus pulmonary syndrome

IGLESIAS AYELÉN; PERIOLO NATALIA,; ALONSO DANIEL; BELLOMO CARLA; MARTINEZ VALERIA

Congreso; LXVI Reunion Anual de la Sociedad Argentina de Inmunología; 2018

Hantaviruses are emerging human pathogens responsible of hantavirus pulmonary syndrome (HPS) in the Americas. Hantaviruses predominantly infect microvascular endothelial cells causing capillary leakage. The hallmark of the disease is the vascular permeability, leading to pulmonary edema in HPS patients. In order to evaluate the role of the immune response on pathogenesis we performed T-cell phenotypic characterization in acute HPS patients (AP), and when possible, longitudinal analysis during convalescence (CONV). We also studied viral load, IgM/IgG titers and kinetics of neutralizing antibodies in blood samples. We obtained control samples from healthy adult volunteers (HV). Almost all patients included presented a severe form of disease.Analysis of PBMCs showed increased TCD8 and decreased TCD4 cells in HPS patients, resulting in alteration of the CD4/CD8 ratio. The phenotypic analysis of T-cell subpopulations showed an average of 44,94% CD8+/CD38+/HLA-DR+ cells (activated phenotype) in AP (average 10,3 days of illness); 13,06% in CONV (average 84,7 days) and 3,49% in HV. TCD4 cells showed 12,85% CD38+/HLA-DR+ in AP; 3,92% in CONV and 1,77 in HV. Statiscal analysis show significant differences between AP and HV. The average for CD8+/CD38+/CD28- was 13,41% in AP; 3,10% in CONV and 0,80% in HV; these differences were not statistically significant. General analysis of relationship between activated CD8 T-cells and viral load did not show any correlation, but analyzing by sex we found positive correlation in women and constant correlation in men. This finding is consistent with higher lethality in women. We also observed differences in activated TCD4 comparing severe and moderate cases.All patients had high IgM/IgG titers in AP. Longitudinal analysis showed decreasing IgM and increasing IgG titers but delay in the development of neutralizing antibodies. Our analysis revealed an activated state of the immune system. Increased T-cell activation markers in acute patients show tendency to normalize during the convalescence.