Journal of Vaccine Research 2024, Vol.14, No.6, 297-306 http://medscipublisher.com/index.php/jvr 298 Based on the above findings, vaccine design targeting conconservative areas can induce a broad immune response and achieve cross-protection against multiple influenza subtypes. This strategy can deal with both progressive antigen drift and sudden antigen transformation, providing the possibility of establishing a long-term immune barrier (Babon et al., 2009; Andrews et al., 2018). 2.2 Functional analysis of T cell subsets Helper T cells are mainly divided into two types: Th1 and Th2. Th1 enhances the activity of CD8+ T cells and macrophages by secreting interferon -γ (IFN-γ), and dominates the cellular immune response. Th2 produces interleukin 4 (IL-4) and IL-10, mainly regulating humoral immunity mediated by B cells. The dynamic balance of the two types of cells directly affects the process of influenza infection and the protective effect of vaccines (Johansson et al., 1987; Powers et al., 1997). Memory T cells (including CD4+ and CD8+ subtypes) are the core components of acquired immunity. They are formed after the initial infection or vaccination, can persist for a long time and expand rapidly, and activate efficient defense during the second infection. This characteristic significantly reduces the severity of diseases with repeated infections (Powers et al., 1997; Babon et al., 2009). 2.3 Antiviral mechanism of T cells During the process of influenza virus infection, antigen-presenting cells (APCs) activate specific T cell responses. CD4+ T cells play a pivotal role by coordinating antibody production and enhancing the function of CD8+ T cells. CD8+ T cells directly clear the infected host cells to block the spread of the virus by recognizing the viral antigens presented by MHC Class I molecules (Powers et al., 1997; Tan et al., 2017). T-cell immunity and humoral immunity form complementary protection: CD4+ T cells assist in the production of high-affinity antibodies, while CD8+ T cells reduce viral load through cytotoxic effects. This collaborative mechanism is crucial for influenza prevention and control and also provides a theoretical basis for the design of broad-spectrum vaccines that integrate humoral and cellular immune responses (Powers et al., 1997; Basha et al., 2011b; Tan et al., 2017). 3 The role of 3-T cell Immunity in Influenza Infection 3.1 Protective mechanism of CD4+ T cells CD4+T cells are the core regulators of anti-influenza immunity and coordinate multiple defense mechanisms. They can not only assist B cells in generating high-affinity antibodies, but also promote the proliferation and memory formation of CD8+ T cells. Furthermore, these cells can enhance the early innate immune response and exhibit direct killing ability. Due to the different previous infection histories of individuals, there are significant differences in the frequency, targeted epitopes and functions of influenza-specific CD4+T cells, further highlighting their key role in immune protection (Figure 1) (Sant et al., 2018). By secreting cytokines such as IFN-γ, IL-2 and TNF-α, CD4+ T cells regulate the CD8+ T cell response and promote the production of neutralizing antibodies. Although they help clear the virus, excessive activation may also lead to immune damage. More importantly, they can form persistent groups of memory cells, laying the foundation for long-term immune protection (Brown et al., 2004). These multifunctional characteristics make CD4+ T cells an important target for vaccine design. 3.2 Antiviral effects of CD8+ T cells CD8+T cells directly alleviate influenza symptoms and shorten the course of the disease by recognizing and eliminating infected cells. They can target viral conserved epitopes (such as nucleoproteins and matrix proteins 1), thereby providing cross-protection against multiple strains (including emerging variants) (Jansen et al., 2019). This broad-spectrum characteristic provides a theoretical basis for the research and development of universal vaccines (Figure 1).
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