Impaired T Cell-dependent Humoral Immune Response Associated with Juvenile-onset Recurrent Respiratory Papillomatosis Progression

Abstract

Whether humoral immunity plays a role in HPV type 6 or 11 virus-mediated Juvenile-onset Recurrent Respiratory Papillomatosis (JORRP) remains unknown. In the present study, serum total IgG level in 44 JORRP patients was significantly decreased compared with that in 40 healthy controls. Moreover, expanded CD3−CD19+ B cells with down-regulation of CD23, CD40, HLA-DR and up-regulation of CD86 expression were found in the peripheral blood of JORRP patients. Flow cytometry analysis of B-cell compartment showed that the frequency of both CD19+CD27hi plasma cells and CD19+CD27+ memory B cells were decreased in JORRP patients. Importantly, although the proportion of circulating CXCR5+PD1hi Tfh cells was not changed, the function of Tfh cells were greatly impaired with reduced ability of IL-21 secretion to promote B cell maturation. Association analysis by the Kaplan-Meier method revealed that IL-21 secreting Tfh cell was positively correlated to the CD27+ B cell subset frequency, the serum IgG level and the frequency of recurrence in JORRP patients, but negatively correlated to the percentage of IgD+CD27− B cell. We concluded that a reduced IL-21 secretion by Tfh cells may limit B cell maturation and antibody production in JORRP patients and Tfh cell-derived IL-21 might be associated with JORRP outcome in clinic.

Impaired HPV-Specific T-Cell Response Characterized with Skewed Cytokine Profile and T-Cell Dysfunction in Juvenile-Onset Recurrent Respiratory Papillomatosis Patients

“…In our previous studies, it has been revealed that children with JORRP exhibited a Th2-biased cytokine pro le [14]. Furthermore, we found that impaired T cell-dependent humoral immune response supported persistent HPV infection in JORRP [15]. These studies exposed the abnormal immune response of T cells to HPV in JORRP.…”

Absence of human papillomavirus in nasopharyngeal swabs from infants in a population at high risk of human papillomavirus infection

“…Since introduction of HPV vaccination (Gardasil ® ) in Australia in 2007, there has been a marked reduction in clinic presentations for genital warts by Aboriginal and Torres Strait Islander Australians aged 21–30 years, 19 but not in older age groups. Surveillance studies continue to monitor new cases of HPV disease and associated types; however, HPV‐related disease remains a concern as does its role in humoral and innate immune impairment 3 . The question of whether HPV plays a role in the very high rates of respiratory infection with immune impairment 20 in Aboriginal infants remains incompletely addressed; however, our results suggest that vertical HPV transmission is an unlikely contributor.…”

“…In infants, the most commonly known manifestation of HPV is respiratory papillomatosis where stridor is often the presenting symptom. However, HPV infection is also associated with impaired humoral and innate immune responses that predispose the child to increased risk of infection 3 . Children may thus also present with recurrent pneumonia, bronchiectasis, and declining pulmonary status 2 .…”

EV PD-L1 Contributes to Immunosuppressive CD8+ T Cells in Peripheral Blood of Pediatric Wilms Tumor

“…T-cell surface marker staining and intracellular cytokine staining for flow cytometry analysis were performed as described previously. 23 , 24 In brief, freshly isolated PBMCs (Ficoll-Hypaque density gradients centrifugation) from fresh whole blood were stimulated with Phorbol-12-myristate-13-acetate (PMA, 50 ng/mL; Sigma-Aldrich) and ionomycin (1 μg/mL; Sangon Biotech) for 4 h. Cell surface staining was performed for 30 min at room temperature followed by fixation and permeabilization using an intracellular staining assay (BD Biosciences) according to the manufacturer's instructions. Cells were then stained with PE-anti-TNFα (Mouse IgG1, clone MAb11), APC-anti-IFNγ (Mouse IgG1, clone B27), or corresponding isotype control antibodies (all from BD Biosciences) at 4 °C for 30 min.…”