Bona Fide Th17 Cells without Th1 Functional Plasticity Protect against Influenza

Area of Science:

• Immunology
• Virology
• Cellular Biology

Background:

• CD4 T cell transcriptional programming is crucial for protection against influenza A virus (IAV), but optimal pathways remain unclear.
• While most IAV-primed CD4 T cells exhibit Th1 characteristics, T-bet-deficient cells retain protective capacity despite reduced Th1 identity.

Purpose of the Study:

• To investigate the roles of T-bet and its paralog Eomesodermin (Eomes) in CD4 T cell responses to IAV.
• To determine the protective capacity of distinct CD4 T cell subsets, particularly Th17 cells, in IAV infection.

Main Methods:

• Utilized gene-deficient mouse models (T-bet deficient, Eomes deficient, and double deficient) to study CD4 T cell differentiation and function.
• Adoptive transfer of effector CD4 T cells (Th1, Th17, Th2) into recipient mice challenged with IAV.
• Assessed viral clearance, host morbidity, and inflammatory responses in infected mice.

Main Results:

• Eomes is essential for residual Th1 attributes in T-bet-deficient cells; double deficiency leads to Th17 and Th2 responses.
• T-bet- and Eomes-deficient Th17 effector cells, but not Th2 cells, conferred protection against lethal IAV infection.
• Th17 cells lacking T-bet and Eomes did not exhibit plasticity towards Th1 phenotype in vivo, unlike wild-type Th17 cells.
• T-bet and Eomes double-deficient mice cleared IAV efficiently without increased morbidity, despite a Th17-biased response.

Conclusions:

• Unadulterated Th17 responses possess potent antiviral capacity against IAV, challenging previous assumptions.
• The findings highlight the protective role of non-plastic Th17 cells and have significant implications for designing effective IAV vaccines.