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T cell

life science Maturity 11-13 Next article →

T cells, also known as T lymphocytes, are a central part of the adaptive immune response. These cells are essential for helping the body recognize and fight specific pathogens. You can distinguish them from other lymphocytes by the T-cell receptor, or TCR, located on their cell surface. This receptor allows the cell to detect specific patterns of invaders.

T cell activation
T cell activation

The journey of a T cell begins in the bone marrow. They originate from c-kit+Sca1+ hematopoietic stem cells. In some cases, they may originate in the fetal liver during embryonic development. These stem cells differentiate into multipotent progenitors, or MPPs. These progenitors can become either myeloid or lymphoid cells. Eventually, they become common lymphoid progenitors, or CLPs. These cells can only turn into T, B, or NK cells. The CLPs then migrate through the blood to the thymus gland to mature.

Once they arrive in the thymus, these immature cells are called thymocytes. Their development involves several complex stages. The earliest cells are called double-negative because they lack both CD4 and CD8 co-receptors. They start as early thymic progenitor (ETP) cells. As they divide, they become double-negative one (DN1) cells. They eventually progress through various DN stages. During this time, they express specific markers like CD2, CD5, and CD7. Eventually, they express both CD4 and CD8, making them double-positive cells.

T cell activation
T cell activation

A critical part of this maturation is building a functional T-cell receptor. The TCR consists of two main parts: the alpha chain and the beta chain. Each cell creates a unique TCR through random variation. This ensures the immune system can recognize many different types of pathogens. First, the thymocyte attempts to create a functional beta chain. It tests this chain against a mock alpha chain. If successful, the cell produces a pre-TCR. This signal allows the cell to move to the double-positive stage. There, it begins to rearrange the TCR alpha locus.

T cell activation
T cell activation

To become active, thymocytes must pass two rigorous tests called selection. Positive selection occurs in the thymic cortex over three to four days. Here, thymocytes are presented with self-antigens on MHC molecules. Only cells that interact well with MHC-I or MHC-II receive a survival signal. Cells that cannot interact strongly enough die from neglect. This ensures the cells have the correct MHC affinity. This process determines if a cell becomes a CD4+ helper cell or a CD8+ killer cell.

Killer T cells surround a cancer cell
Killer T cells surround a cancer cell

Next, the cells undergo negative selection in the thymic medulla. This process is vital for preventing autoimmune responses. In the medulla, cells are presented with self-antigens by medullary thymic epithelial cells, or mTECs. These mTECs must be AIRE+ to express these specific antigens. If a thymocyte binds too strongly to a self-antigen, it receives a signal to die. This prevents the immune system from attacking the body's own cells. Some of these cells are instead chosen to become regulatory T cells.

The selection process is extremely strict. About 98% of all thymocytes fail and die during development. Only about 2% survive to leave the thymus as mature naive T cells. As people age, the thymus begins to shrink by about 3% each year. This causes a fall in the production of new naive T cells. Consequently, older people rely more on the expansion of existing cells.

Mature T cells are grouped into subsets based on their specific functions. CD8+ T cells are known as killer or cytotoxic T cells. They can directly kill cancer cells or virus-infected cells. They also use signaling proteins called cytokines to recruit other cells. CD4+ T cells are known as helper T cells. They activate B cells and other cytotoxic T cells to create a larger response. Different subtypes, like T-helper1 or T-helper2, are defined by the cytokines they secrete.

Regulatory T cells, or suppressor T cells, provide a critical mechanism of tolerance. They help the immune system distinguish between invading cells and "self" cells. This prevents the immune system from reacting against the body's own tissues. However, cancer cells can sometimes co-opt these regulatory cells. If they do, the cancer can prevent the immune system from recognizing the tumor. This allows the tumor to grow without being attacked.

Killer T cells surround a cancer cell
Killer T cells surround a cancer cell
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CD4+ T cell subsets.pdf
File:Killer T cells surround a cancer cell.png
Killer T cells surround a cancer cell.png
File:T cell activation.svg
T cell activation.svg
File:HIV-infected T cell (6813384933).jpg
HIV-infected T cell (6813384933).jpg
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