What Are CD8+ T lymphocytes?
T lymphocytes, or T cells, are the main cells of adaptive immunity. They are involved in multiple immune responses, including producing cytokines, destroying infected cells, and triggering other immune system components to regulate immune reactions.
T cells originate from the hematopoietic stem cells in the bone marrow. They are derived from the common lymphoid progenitor and mature in the primary lymphoid organ: the thymus. T lymphocytes divide and differentiate into cytotoxic, helper, regulatory T cell, or memory T cells in this organ. They also undergo thymic selection to eliminate autoreactive cells in a process known as central tolerance.
In this article, we will cover the basic biology of CD8+ T lymphocytes, including their differentiation, cytokines-mediated cell signaling pathways, epigenetic alterations of genes, and activated transcription factors involved.[1] We will also explain the current research applications for these immune cells in developing new therapies.
CD8+ T Lymphocytes
The CD8+ T lymphocytes are also known as cytotoxic T cells (CTLs) and killer T cells. They possess the ability to kill any virus-infected cell or tumor cell. They also trigger cytokine-mediated recruitment of other immune cells.
CD8+ T cells recognize antigens presented by class I MHC molecules. Upon activation, they become cytotoxic T cells and release anti-viral cytokines, i.e., TNF-α (tumor necrosis factor-alpha), IFN-γ (interferon-gamma), and other cytotoxic molecules that kill infectious particles. Shortly after the removal of the antigen, some effector cytotoxic T cells die via apoptosis; while the remaining surviving CTLs differentiate into memory CD8+ T cells.[2]
CD8+ T Cell Subsets
Cytotoxic T cells differentiate into the following subsets:
- Stem cell-like memory T cells (T SCM): antigen-specific and possess prolonged half-life and self-renewal ability to reconstitute effector cytotoxic T cells upon antigen re-exposure.
- Central Memory T cells (T CM): guard the lymph nodes, recognize and react against known pathogens.
- Effector memory T cells (T EM): these memory T cells are found in the tissues and the peripheral circulation.
- Effector T cells (T EFF): these CD8+ T cells are short-lived and can directly destroy infected cells.[3]
The Cross-Talk between CD8+ T Lymphocytes and Natural Killer Cells
CD8+ T cells extensively communicate with other immune cells to form a synergistic immune response. Natural killer (NK) cells help cytotoxic T cells proliferation and differentiation via a crosstalk through the release of costimulatory molecules and cytokines. They synergistically exert cytotoxic effects with CD8+ lymphocytes against target cells; however, T cells act through a different mechanism where they directly target and kill cancer or virus-infected cells by releasing perforins and granzymes or by secreting pro-inflammatory cytokines.
Additionally, NK cells interact and influence the maturation of dendritic cells (DCs) by producing TNF-α and IFN-γ, thus promoting CD8+ cytotoxic T cell immune responses. This cell-cell crosstalk results in an amplified effector cooperativity against cancerous or other infected cells.[4]
CD8+ Cytotoxic T Cell Activation Process
CD8+ T cell Uses in Research
Anti-cancer therapies
Many CD8+ T cell therapies are currently designed and investigated to combat various cancers, such as adoptive CD8+ T cell therapy or anti-cancer therapy (ACT). In this therapy, tumor-specific cytotoxic T cells are taken from patients, grown and expanded in-vitro using cell culture, and then infused into patients.[5]
Moreover, many immunotherapies-based anti-cancer approaches are also devoted to increase, maintain, and excite tumor-responsive CD8+ T cell reactions.[6]
The anti-viral potential of CD8+ T cells
Considering the remarkable cytotoxic abilities of CD8+ T cells, new anti-viral therapies are being introduced with other immunoregulatory elements.
Virus-specific CD8+ T cells are introduced along with antibodies to develop ideal immunity against viruses in affected individuals. This approach may also help in vaccine development against many viruses in the future.[7]
Autoimmune diseases
In autoimmune diseases, CD8+ T cell activation and differentiation are influenced by epigenetic changes. These altered epigenetic patterns occur in essential transcription factors, cytokines, and other regulatory components.
Therefore, by regulating the epigenetic pattern of these genes, CD8+ T cells can be effectively targeted to develop potential therapeutics against autoimmune diseases.[8]
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