T cell activation in patients with severe hantavirus pulmonary syndrome from Argentina

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

Leuven,

Congreso; 11TH INTERNATIONAL CONFERENCE ON HANTAVIRUSES; 2019

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 presented a severe form of disease. Analysis of PBMCs showed increased TCD8 and decreased TCD4 cells in HPS patients after 4 days of illness onset, resulting in alteration of the CD4/CD8 ratio. The phenotypic analysis of T-cell subpopulations showed an average of 39.1% CD8+/CD38+/HLA-DR+ cells (activated phenotype) in AP (average 9.6 days of illness); 12.3% in CONV (average 77.7 days) and 2.3% in HV. TCD4 cells showed 9.4% CD38+/HLA-DR+ in AP; 4.1% in CONV and 1.1% in HV. Statistic analysis show significant differences between AP and HV (ANOVA "Kruskal-Wallis test"). The average for CD8+/CD38+/CD28- was 13.41% in AP; 3.10% in CONV and 0.80% in HV (differences were not statistically significant). On the other hand, analysis of inhibitorymarkers PD1 and CTLA4 on T-cells did not show over-expression in AP. Activated CD8T-cells phenotype did not show any correlation with viral load or severity grade. It is noteworthy that, in general, viral load was stable in blood samples during the acute phase, at discharged from hospital, and during early convalescence (up to 126 days after fever onset). Furthermore, the CD8T-cells activated phenotype persisted in elevated values at least up to 1 month after illness onset. 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. Actually intracytoplasmic molecules are being analyzed in order to evaluate T-cell functionality.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.