T cells: activation, function, types, and dysregulation

T cells, or T lymphocytes, are the cornerstone of the adaptive immune system and are an important part of protecting the body from a variety of threats, including infection, cancer, and other harmful agents. These specialized white blood cells are essential for recognizing and responding to specific antigens. They originate from hematopoietic stem cells in the bone marrow, mature in the thymus, and then circulate through the lymphatic system and blood. Understanding the complex functions and roles of T cells in the immune system can provide insight into their important contributions to health and disease.

T cell maturation

T cells begin their journey in the bone marrow, where hematopoietic stem cells give rise to progenitor T cells. These progenitor cells then migrate to the thymus, a specialized immune organ, where they undergo a rigorous maturation process. In the thymus, T cells produce T cell receptors (TCRs), which are critical for recognizing specific antigens. The maturation process includes positive and negative selection to ensure that T cells can distinguish between self and non-self antigens. T cells that react strongly to self-antigens are usually eliminated, while those that recognize foreign antigens are allowed to mature.

Signal 1: Antigen recognition

After leaving the thymus, mature T cells circulate in secondary lymphoid organs such as lymph nodes and spleen in search of their specific antigens. Initial activation occurs when T cells recognize antigens presented by major histocompatibility complex (MHC) molecules on the surface of antigen-presenting cells (APCs).

• CD4+ helper T cells: These cells recognize antigens presented by MHC class II molecules. The TCR binds to the antigen-MHC class II complex, and the CD4 molecule on the T cell stabilizes this interaction by binding to the MHC class II molecule.
• CD8+ cytotoxic T cells: These cells recognize antigens presented by MHC class I molecules. The TCR binds to the antigen-MHC class I complex, and the CD8 molecule on the T cell provides additional stability.

This antigen recognition typically occurs in secondary lymphoid organs, where T cells are primed to respond to a specific threat.

Signal 2: Common stimulation

To be fully activated, T cells require additional signals beyond the antigen-MHC interaction. These secondary signals ensure a strong and regulated immune response:

• Helper T cells: CD28 on T cells combines with B7.1 (CD80) or B7.2 (CD86) on APC to provide necessary costimulatory signals for T cell activation. This interaction promotes T cell proliferation and survival. To prevent excessive immune responses, CD28 stimulation leads to the production of CTLA-4 (CD152), which competes with CD28 for binding to B7 molecules and modulates immune responses.
• Cytotoxic T cells: Although cytotoxic T cells are less dependent on CD28, signals from other costimulatory molecules such as CD70 and 4-1BB (CD137) are also required.

In addition, T cells also receive survival signals from molecules such as ICOS, 4-1BB and OX40. These are expressed only after pathogen recognition, ensuring that T cells are activated only by APCs that encounter and respond to the pathogen. Without these signals, T cells become unresponsive, preventing inappropriate activation.

Signal 3: Cytohormone signaling

After receiving antigen-specific and costimulatory signals, T cells receive further instructions in the form of cytokines. These cytokines direct the type of immune response that T cells will produce:

• Helper T cells: The cytokine environment guides the differentiation of helper T cells into various subpopulations:
  • Th1 cells: Induced by IL-12, these cells enhance cellular immunity and effectively fight intracellular pathogens.
  • Th2 cells: Induced by IL-4, these cells help fight extracellular pathogens and participate in allergic reactions.
  • Th17 cells: Induced by IL-6 and IL-23, these cells play a role in the inflammatory response and protection against certain extracellular pathogens.

These differentiated T cells then migrate to the site of infection or inflammation. Local cells at the site, such as neutrophils and mast cells, release additional cytokines and chemokines to further activate and recruit T cells.

Types of T cells

1. Helper T cells (CD4+ T cells):
   • Function: Helper T cells coordinate immune responses by releasing cytokines that stimulate other immune cells, including B cells and cytotoxic T cells.
   • activation: These cells bind to antigens presented by MHC class II molecules on antigen-presenting cells (APCs).
2. Cytotoxic T cells (CD8+ T cells):
   • Function: Cytotoxic T cells directly kill infected cells or cancer cells by inducing apoptosis.
   • activation: They recognize antigens presented by MHC class I molecules and destroy target cells.
3. Regulatory T cells (Treg):
   • Function: Regulatory T cells help maintain the balance of the immune system by suppressing excessive immune responses and preventing autoimmune reactions.
   • activation: They regulate immune activity and prevent attacks on healthy tissue.
4. memory T cells:
   • Function: After an immune response, some T cells become memory cells and persist in the body. They “remember” previous pathogens and enable the immune system to respond faster and more effectively when exposed to the pathogen again.

How T cells work

1. Antigen presentation:
   • APC presents antigens on its surface via MHC molecules. The type of MHC (class I or class II) determines whether helper T cells or cytotoxic T cells are activated.
2. T cell activation:
   • T cells possess unique receptors (TCRs) that bind to antigen-MHC complexes. This combination ensures that T cells are properly activated to target specific pathogens.
3. clonal expansion:
   • After activation, T cells undergo clonal expansion, producing large numbers of copies of themselves to effectively fight pathogens.
4. Effector and memory functions:
   • Activated T cells, called effector cells, are responsible for eliminating pathogens. After infection, memory T cells continue to provide long-term immunity.

location and maturity

• marrow: T cells originate from hematopoietic stem cells in the bone marrow.
• Thymus: T cells migrate to the thymus to mature, where selection occurs to ensure that they can recognize MHC molecules and distinguish self from non-self.
• lymphoid tissue and blood: Mature T cells circulate in lymphoid tissues such as the spleen, lymph nodes, and tonsils, as well as in the blood, ready to respond to pathogens.

Conditions and diseases affecting T cells

1. acute lymphoblastic leukemia (ALL): A cancer that starts in the bone marrow and affects T cells. It causes the overproduction of immature lymphocytes, which impairs the production of normal blood cells.
2. Hodgkin lymphoma: Cancers of the lymphatic system involving T cells. It is characterized by the presence of Reed-Sternberg cells and can affect lymph nodes and other organs.
3. T cell lymphoma: A variety of cancers that originate in T cells and can affect a variety of tissues. These include peripheral T-cell lymphoma and cutaneous T-cell lymphoma.
4. DiGeorge syndrome: A genetic disorder caused by a deletion of chromosome 22, resulting in underdevelopment or absence of the thymus. This condition impairs T cell production and function.
5. HIV/AIDS: HIV mainly targets and destroys helper T cells (CD4+ T cells), causing damage to the immune system. If not treated in time, it will progress to AIDS.
6. autoimmune diseases: Diseases in which T cells mistakenly attack the body’s own tissues, such as multiple sclerosis (attacking the central nervous system) and type 1 diabetes (attacking insulin-producing cells in the pancreas).

Test and monitor

1. T cell count:
   • Measure the number of T cells in the blood. Normal ranges vary by type and laboratory, but are typically between 500 and 1,200 cells/mm3 for CD4 counts and between 150 and 1,000 cells/mm3 for CD8 counts.
2. CD4 to CD8 ratio:
   • Assess the balance between helper T cells and cytotoxic T cells. Abnormal ratios may indicate a problem with the immune system, such as a low CD4 count in HIV infection.
3. special test:
   • For HIV-infected patients, monitoring T cell numbers is critical to assess immune function and treatment effectiveness. Specialized testing may include flow cytometry to analyze T cell subsets and their function.

Enhance T cell health

Supports T-cell function and overall immune health:

1. balanced diet:
   • Consuming a variety of nutrients, including vitamins A, C, D, and E, as well as minerals like zinc and selenium, can support immune function and T-cell health.
2. exercise regularly:
   • Engaging in moderate physical activity can enhance blood circulation and overall immune function, helping to make your T cells healthier.
3. adequate sleep:
   • Aim for 7-8 hours of quality sleep every night to ensure normal immune function and T-cell regeneration.
4. Vaccination:
   • Continuing to receive recommended vaccinations can help prevent infections that may challenge the immune system and T cells.
5. Avoid harmful substances:
   • Limiting alcohol intake and avoiding smoking and vaping can help maintain a healthy immune system and support T-cell function.
6. health:
   • Frequent hand washing and use of hand sanitizer can prevent infection and reduce the burden on the immune system.

T cell research and isolation

Advanced technologies such as microbubble technology are revolutionizing T cell research and treatment. These methods allow researchers to isolate and study T cells with high precision. This research is critical for:

1. gene expression studies:
   • Studying T cell behavior and function at the molecular level can provide insights into how T cells respond to infections and other stimuli.
2. vaccine development:
   • Assessing T cell responses to new vaccines could help develop more effective immunizations.
3. adoption T cell therapy:
   • This therapy involves boosting T cells in the laboratory to treat cancer and other diseases. Modified T cells are reintroduced into the patient to target and destroy cancer cells or other pathogens.

in conclusion

T cells are an integral part of the immune system and are critical for fighting infections, regulating immune responses and providing long-term immunity. Their complex roles include recognizing specific antigens, undergoing maturation and activation, and maintaining immune system balance. Understanding T cell functions, types, and associated diseases is critical to advancing medical research and improving treatments. Continued research into T cell biology and technology promises to lead to new treatment strategies and better management of various conditions.

refer to

• Janeway, CA, Travers, P., Walport, M., & Shlomchik, MJ (2001). Immunobiology: The immune system in health and disease (5th ed.). Garland Science.
• Miller, J. F. A., & Matzinger, P. (2002). “The role of T cells in immune responses.” immunity16(1), 1-12. DOI: 10.1016/S1074-7613(02)00004-4
• Dudley, ME, and Rosenberg, SA (2003). “Adoptive Cell Therapy for Cancer: A Review.” immunological review193, 50-63. DOI: 10.1034/j.1600-065x.2003.00075.x
• Germain, RN (2002). “The role of T cell development and antigen presentation.” Nature Reviews Immunology2(6), 423-434. DOI: 10.1038/nri832
• Zhou, X., and Liao, W. (2018). “Regulatory T cells and their role in the immune system.” Frontiers of Immunology9,2456. DOI: 10.3389/fimmu.2018.02456