IL-4/IL-4 Ab complex enhances the accumulation of both antigen-specific and bystander CD8 T cells in mouse lungs infected with influenza A virus

• Published in: Laboratory animal research Vol. 39; no. 1; pp. 32 - 10
• Main Authors: Park, Hi Jung, Choi, Eun Ah, Choi, Sung Min, Choi, Young-Ki, Lee, Jae Il, Jung, Kyeong Cheon
• Format: Journal Article
• Language: English
• Published: London BioMed Central 01.12.2023; BMC; 한국실험동물학회
• Subjects: Biomedical and Life Sciences; CD8 T cells; CXCR3; Influenza; Interlukin-4; Life Sciences; Virtual memory; 수의학; Interlukin-4; Virtual memory; CXCR3; Influenza; CD8 T cells
• ISSN: 2233-7660; 1738-6055; 2233-7660
• DOI: 10.1186/s42826-023-00183-2

Background Unlike conventional T cells, innate and virtual-memory CD8 T cells in naïve mice acquire their memory phenotypes and functions in the absence of antigenic encounters in a cytokine-dependent manner. The relevant cytokines include interleukin-4 (IL-4), type I interferon, and interleukin-15 (IL-15). Moreover, exogenous IL-4 can also induce de novo generation and/or expansion of the virtual-memory CD8 T cell population. In this study, we investigated whether exogenous IL-4 could enhance the immune response to a viral infection. Results In vivo administration of IL-4 and an anti-IL-4 antibody complex (IL-4C) increased CXCR3 expression in both memory and naïve phenotype CD8 T cells in the absence of antigenic stimulation, and protected mice from lethal influenza infection. Flow cytometric analysis of lung-infiltrating immune cells on day 5 after virus infection revealed higher numbers of antigen-specific and bystander CD8 T cells in IL-4C-treated mice than in control mice. In particular, the bystander CD8 T cells were a naïve or evident memory phenotypes. Crucially, an anti-CXCR3 blocking antibody abrogated this IL-4C effect, reflecting that the increased accumulation of CD8 T cells in the lungs after IL-4C treatment is dependent on CXCR3. Conclusions These data demonstrate that exogenous IL-4C plays a protective role by enhancing CXCR3-dependent migration of CD8 T cells into influenza-infected lungs.