Human T Cell Activation

T cell activation takes place when the T cell encounters the specific antigen-MHC complexes that match its T cell receptor. This catalyzes the launch of a targeted immune response. Human T cells become activated by interacting with transmembrane proteins on the surface of antigen-presenting cells (APCs) that present specific peptide antigens on their cell surface and express other cell surface proteins called costimulatory molecules. 

Once fully activated, the antigen-specific T cell population grows rapidly through T cell expansion as cells divide, differentiate, and secrete their effector molecules. This clonal expansion and differentiation push the immune response forward to clear the pathogen. Once the infection has been quelled, the inflammatory response is contracted and the majority of the specific T cell population undergoes apoptosis. A few memory lymphocytes remain in the bloodstream, in case of reexposure or reinfection. 

T cells primarily identify and eliminate foreign particles that humans encounter throughout their lives. T cells are one of the essential components of our adaptive immune system because of their unique nature. T cells are only activated by their distinct antigen. Many T cells will never encounter their cognate antigen and will spend their entire lifecycle naive and inactive. 

When a T cell is activated by a novel pathogen, the consequential inflammatory response is specially crafted by the T cells for that particular intruder. After the pathogen is cleared, a small portion of the responding cells develops into memory cells to protect against future exposures. This process builds immune system resilience over a lifetime of exposure to new threats. 

Once humans reach a certain age, lymphocyte count becomes a significant indicator of immune health and strength. In adulthood, human T cells maintain inflammatory homeostasis and address chronic exposures. High lymphocyte count can also indicate instances of autoimmune diseases and cancers. T cells that undergo uncontrolled activation can cause inflammatory episodes or autoimmune disease, and T cells refusing to die can indicate the development of cancer. 

Naive T Cell Activation

Naive T cells are precursors for effector and memory T cells. Caught between the stages of maturation and activation, naive T cells circulate the bloodstream in search of their unique antigen. Pre-activated with a unique T cell receptor (TCR) ready for activation, most naive T cells will live and die without ever becoming activated.

Naive T cells are activated by an APC, causing them to proliferate and differentiate into the T cell types needed most in the immune response. Once the infection has been quelled, almost all active T cells die, except for a few memory T cells which can either circulate or reside in lymphoid tissue in case of reexposure. This phenomenon fuels new immunities as humans encounter new infections and pathogens. 

How Are T Cells Activated?

The T cell receptor on the surface of the T cells must recognize and bind to a matching peptide-MHC complex on the surface of an APC to trigger T cell activation. Additional activating signals generated through recognition of activating cytokines and the interaction of cell surface costimulatory molecules with their ligands provide the second and third signals needed for optimal T cell activation.  The MHC complex plays an integral role in T cell activation, expansion, and regulation. APCs can acquire these specific antigens by engulfing and partially degrading the invading pathogen at the site of the infection and encounter. The APC will export fragments of the destroyed microbe to the cell’s surface, displaying it for recognition by an accompanying T cell to launch a targeted attack. Alternately, infected cells are capable of presenting pathogen–derived proteins made within the cell itself. 

Once a naive T cell finds the distinct antigen required for activation, an extensive proliferation of antigen-specific T cells is induced. This reaction creates antigen-specific CD4 helper T cells or CD8 cytotoxic T cells ready to launch a targeted attack on the progressing infection. The magnitude of this expansion is enormous; cytotoxic T cells multiply by a factor of 50,000. 

T Cell Activation—Markers

Signaling through both CD28 and TCR/CD3 is required for successful T cell activation. The costimulatory molecule CD28 augments the T cell receptor activating signals, while CD3 is the part of the TCR that transfers activation signals into the cell to trigger the proliferation and differentiation of the activated T cell. Costimulation through CD28 regulates the subsequent inflammatory response by boosting the production of cytokines, guiding T cell differentiation and survival. 

T Cell Activation—Cytokines

Cytokines are one of the major tools of effector T cells for communication and mediating inflammation. The different types of effector T cells have unique associated cytokine types. Cytokines are small proteins that have activating or suppressive effects on other cells. One subset of pro-inflammatory cytokines works on T cells to regulate the intensity and duration of an inflammatory response by reducing the threshold of antigen concentrations to stimulate further activation. 

Cytokines, or the lack thereof, are also responsible for the collective cell death that occurs once the infection has been destroyed. This ability is one of the reasons that cytokines can be critical tools for fighting cancer within the body and in cancer research. 

TCR Stimulation

The TCR is a complex made up of two T cell receptor chains (alpha and beta or gamma and delta) and multiple CD3 chains. This complex serves to both recognize specific foreign antigens in complex with MHC molecules and propagate activation signals into the cell. 

Stimulation of TCR leads to proliferation, differentiation, cytokine production, and apoptosis. Signaling cascades from the stimulation of TCR regulates T cell development and activation. 

Can T Cells Be Artificially Activated?

Yes, there are several in-laboratory approaches for T cell activation. This practice provides a controlled method for the study of T cell biology or to prime therapeutic T cell populations. This can be facilitated through the innovation of APC-mimetic scaffolds (APC- ms), which artificially present chemical signals to T cells to mediate activation and rapid T cell expansion. More often, however, activation is achieved in vitro through the use of soluble or particle-bound antibodies against CD3 and CD28 that lead to the generation of activation signals. 

Types of Activated T Cells

Activated Cytotoxic T Cells

During viral infections, many “T cells are activated in a T cell receptor-independent and cytokine-dependent manner”. This is referred to as “bystander activation.” Even though bystander T cells are not relevant to the pathogen, they still impact the immune response’s course to the infection. 

Activated Helper T Cells

Once activated, helper T cells play several roles in the inflammatory response. Helper T cells signal specific instructions to other cells via cytokines and other effector molecules. They can also directly activate cytotoxic T cells to kill or B cells to produce antibodies.

Where Does Lymphocyte Activation Occur?

Lymphocyte activation transpires in the secondary lymphoid organs when the cell locates its predetermined antigen. Lymphocytes circulate through the secondary lymphoid organs: the spleen, lymph nodes, tonsils, and special lymphoid structures within mucosal tissues. 

Why Is Human T Cell Activation Necessary?

Human T cell activation is imperative to successful adaptive immune response and allows for the resilience of human immunity to developing diseases. Human T cells are therefore an important subject for study and can help further understand the mechanisms underlying effective immune responses. 

Akadeum Products for T Cell Activation and Activated T Cell Isolation

Isolate large numbers of highly pure activated T cells for any downstream applications. Akadeum’s Human T Cell Isolation Kit delivers high-purity populations of activated T cells when collected during T cell expansion. 

The use of our revolutionary microbubbles enriches the initial peripheral blood mononuclear cell (PBMC) material for significantly reduced sort times. The gentle nature of the negative selection isolation protocol is ideal for fragile cell populations, helping to defend the health and physiology of the isolated cells.

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