Group 2 innate lymphoid cells mediate the activation of CD4+ T cells and aggravate Th1/Th2 imbalance via MHC II molecules during respiratory syncytial virus infection

Background: Respiratory syncytial virus (RSV), as an important worldwide pediatric respiratory pathogen, can cause pneumonia and bronchiolitis in infants and young children. CD4 + T cells play a crucial role in RSV-induced airway inflammation. However, the underlying mechanism of CD4 + T cell activation during RSV infection is not fully understood. Methods The proliferation and activation of CD4 + T cells in the lungs of RSV infected BALB/c mice were measured by flow cytometry. RSV-induced airway inflammation was determined by HE staining and the inflammatory cells in bronchoalveolar lavage fluids (BALF) were counted. The protein levels of IL-4, IL-5, IL-13, and IFN-γ in the supernatant of BALF were detected by ELISA. The mRNA levels of IL-4, IL-5, IL-13, and IFN-γ in the lung homogenates were analyzed by real-time PCR. The expression of major histocompatibility complex II (MHCII), CD80 and CD86 on pulmonary ILC2s were measured by flow cytometry and real-time PCR. Results RSV infection may promote the differentiation and activation of CD4 + Th2 cells, resulting in imbalance of Th1/Th2 in the lung tissues. Depletion of CD4 + T cells can obviously reduce airway inflammation caused by RSV infection. Adoptive transfer of pulmonary ILC2s significantly enhanced the number of pulmonary CD4 + T cells and promoted their differentiation to Th2. In fact, RSV infection increased the expression of MHC II and B7 molecules on the surface of pulmonary ILC2s. In vitro co-culture experiments showed that ILC2s may act as a promoter to promote the expansion and differentiation of RSV-infected naïve CD4 + T cells. However, blocking the interaction between ILC2s and CD4 + T cells with anti-MHC II mAbs significantly reduced CD4 + T cell expansion and increased the Th1/Th2 ratio of CD4 + T cells. Conclusions Our data suggest that pulmonary ILC2s may function as antigen-presenting cells to induce the activation of CD4 + T cells through MHC II pathway during RSV infection.