Th immune response in enhanced RSV disease

ACOSTA, PL; WIMMENAUER, V; BRUM-ORNELAS C; SCALZO PM; LAWRENCE A; HIJANO DR; NEWCOMB D; PRINCE G; PEEBLES RS; POLACK FP

Nashville

Simposio; Pediatrics infectous diseases reatreat 2011; 2011

Objective: Determine the role of T helper type 17 lymphocyte in the enhanced disease (ERD) caused by respiratory syncytial virus (RSV) in toddlers immunized with an inactivated RSV vaccine.   Study Design: Mice: 4-6 week old female BALB/c and C57BL/6 mice. Immunization: FIRSV 1x105 pfu, RSV 1x105 pfu, PBS (placebo) administered in footpad. Challenge: 60 days post-immunization, mice were challenged with RSV A2 106 pfu intranasally. Histopathology: Lung sections were stained with H&E and PAS. Cytokine responses and Th transcription factors were assayed in bronchoalveolar lavage fluids and regional lymph nodes by immunoasssay and real time RT-PCR. Lung sections from toddlers who died of ERD in 1967 were stained by immunohistochemistry.   Results:  Inactivated RSV vaccine enhances IL-17 production in regional lymph nodes after immunization compared to the response elicited by RSV or placebo. Th17 inmune response is enhanced in the lungs of mice with ERD. ROR-ãt (Th-17 master trancription factor) levels are increased in the lungs of mice with ERD. AHR and bronchipneumonia are significantly decreased in mice treated with anti-IL-17 antibody. IL-17 positive cells are abundant in the lungs of toddlers killed by ERD in 1967.   Conclusions:  Th-17 cells play a key role in enhanced RSV disease.