Cytotoxic T Cells: Kill, Memorize, and Mask to Maintain Immune Homeostasis.

Homeostasis must be maintained for the healthy living of an organism. In addition to physiological and anatomical homeostasis, the maintenance of the immune system, called immune homeostasis or immunohomeostasis, is critical for overall well-being and general homeostasis. CD8 cytotoxic T cells/lymphocytes (CTLs) are crucial components of the adaptive immune systems of all vertebrates with a thymus. Hence, the thymus is an essential primary lymphoid organ (PLO) for developing T cell-mediated immunity (TCMI) that comprises CD4 helper T cells (Th) cells and their subtypes, such as Th0 (naïve helper T cells), Th1 (pro-inflammatory Th cells that secrete IFN-γ), Th2 (secrete type 2 cytokines, such as IL-4, IL-5, IL-6, IL-10, and IL-13), Th9 (secrete IL-9), Th17 (secrete IL-17), Th22 (secrete IL-22), follicular Th cells (T, secrete IL-21), regulatory T cells (T), and CD8CTLs. The current article explores the critical role of CD8CTLs in the maintenance of immune homeostasis. The role of the thymus (PLO) in generating and regulating CD8CTLs, as well as mobilizing them to distant lymph nodes (LNs) and the spleen, which are referred to as secondary lymphoid organs (SLOs) and target organs, is discussed in section two of the article. The subsequent third section discusses the role of CD8CTLs' cytotoxic and immunoregulatory action to maintain immune homeostasis during infection and other inflammatory conditions. Moreover, they mask themselves to different cell types, like Th cells, such as Tc2s, Tc9s, Tc17s, and Tc22s, to maintain immune homeostasis. CD8CTLs also behave as T to exert their immunoregulatory functions. In addition to conventional CD8CTLs, granzyme K (GzmK)CD8CTLs and CD4CTLs with their cytotoxic action to maintain immune homeostasis have also been discussed. The next section discusses cell-cell (APC-CD8CTL) interactions that not only increase the cytotoxic functions of CD8CTLs but also program APCs to support their cytotoxic functions. These CD8CTLs secrete different cytokines (IFN-γ and IL-10) and cytotoxic molecules (perforin and Gzms), which exert immunoregulatory actions to maintain immune homeostasis. The article concludes with a future perspective and a conclusion section, highlighting the critical need to understand CD8CTLs' cytotoxic and immunoregulatory functions in maintaining immune homeostasis across various diseases, including those with newly identified roles for CD8CTLs.