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Original Author(s): Alliya Ghanchi
Last updated: 2nd September 2021
Revisions: 17

Original Author(s): Alliya Ghanchi
Last updated: 2nd September 2021
Revisions: 17

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T cells (also called T lymphocytes) are major components of the adaptive immune system. Their roles include directly killing infected host cells, activating other immune cells, producing cytokines and regulating the immune response.

This article discusses T cell production, the different T cell types and relevant clinical conditions.

Production of T cells

T lymphocytes originate from haematopoietic stem cells within the bone marrow. Some of these multipotent cells subsequently become lymphoid progenitor cells that leave the bone marrow and travel to the thymus via the blood.

Once in the thymus, T lymphocytes undergo a selection process in which the majority of developing T cells (called thymocytes) will not survive. During this process, thymocytes with receptors for self-antigens receive negative signals and are removed from the repertoire.

Each T lymphocyte has a T cell receptor (TCR) which is specific to a particular antigen. T lymphocytes that survive thymic selection will mature and leave the thymus. After that, They circulate through peripheral lymphoid organs, ready to encounter their cognate antigens and become activated. The thymus atrophies as we age and so produces fewer naïve T lymphocytes over time.

Development of t cells

Fig 1 – Diagram demonstrating immune cells and the progenitor cells they are derived from.

T cell types

Naïve T lymphocytes are cells that have not yet encountered their specific antigen. In peripheral lymphoid organs, naïve T lymphocytes can interact with antigen-presenting cells (APCs), which use MHC molecules to present antigen. Once the T lymphocytes recognise their specific antigens, they proliferate and differentiate into one of several effector T lymphocyte subsets. Effector T lymphocytes interact with host cells (rather than the pathogen) to carry out their immune function.

T lymphocytes use co-receptors to bind to the MHC molecules. Co-receptors can be either CD4 or CD8. CD proteins help to differentiate major groups of effector T lymphocytes. Naïve CD8+ T lymphocytes will become cytotoxic T lymphocytes. Alternatively, CD4+ T lymphocytes will become T helper lymphocytes, each of which specialised for particular tasks.

Cytotoxic T cells

Cytotoxic T lymphocytes kill their target cells primarily by releasing cytotoxic granules into the target cell. These cells recognise their specific antigen (such as fragments of viruses) only when presented on MHC Class I molecules present on the surface of all nucleated cells.

MHC Class I molecules interact with CD8 on the cytotoxic T cells. Cytotoxic T cells require several signals from other cells like dendritic cells and T helper cells to be activated.

Their main function is to kill virally infected cells, but they also kill cells with intracellular bacteria or tumorous cells.

T-Helper Lymphocytes

T helper cells (Th) have a wide range of effector functions and can differentiate into many different subtypes, such as Th1, Th2, Th17, TfH cells and regulatory T cells.

They become activated when they are presented with peptide antigens on MHC Class II molecules. These are expressed on the surface of APCs. MHC Class II molecules interact with CD4 on the T helper cells, which helps identify this cell type.

CD4+ T cell functions include activating other immune cells, releasing cytokines, and helping B cells to produce antibodies. They help to shape, activate and regulate the adaptive immune response.

Memory T cells

Antigen-specific, long-lived memory T lymphocytes form following an infection. Memory T lymphocytes are important because they can quickly proliferate into large numbers of effector T lymphocyte upon re-exposure to the antigen and have a low threshold for activation.

They provide the immune system with memory against previously encountered antigens. Memory T lymphocytes may either be CD4+ or CD8+.

Activation of t cells

Fig 2 – Diagram summarising T cell activation.

Type Stimulus cytokines Transcription factor Function Effector molecules Target organisms
CD8 Cytotoxic T cells IL-12

IL-18

T-bet

Blimp1

Kills virus-infected cells. Granzyme

Perforin

TNF-α

Fas ligand

Viruses
CD4 TH1 cells IL-12

IFN-γ

IL-2

T-bet Activates macrophages.

 

Helps cytotoxic T-cells.

 

Provides B-cell help for antibody production

IL-12

IFN-γ

IL-2

Intracellular (mycobacteria, listeria, leishmania) and extracellular bacteria.

Fungi.

TH2 cells IL-4 GATA3

STAT6

Provide help to B cells for antibody production-  especially IgE antibodies.

 

Activates eosinophils and mast cells.

IL-4

IL-5

IL-13

Helminth

Extracellular Parasites

 

TH17 cells IL-6

IL-21

TGF-β

ROR-γT

STAT3

Enhance neutrophil response.

 

Improve epithelial barrier function.

IL-17

IL-21

IL-22

IL-26

IL-6

Extracellular bacteria (e.g. Salmonella enterica)
TFH cells IL-6

IL-21

 

Bcl6 Germinal centre formation.

 

B cell antibody isotype switching.

 

Antibody affinity maturation.

 

Enables B cells to develop into plasma cells for  Long term humoral immunity

IL-10

IL-21

IL-4

T regulatory cells TGF-β

 

Foxp3 Suppresses other immune cells, particularly CD4+ and CD8+ responses. TGF-β

IL-10

CTLA-4

Clinical Relevance – Severe Combined Immune Deficiency (SCID)

SCID is a group of primary immunodeficiencies with defects in T and B cell numbers and/or function. Individuals with SCID are prone to recurrent infections, sepsis and failure to thrive.

SCID can result from defects in many genes, although the most common defect is X-linked.

The best treatment for SCID is a bone marrow transplant.

Clinical Relevance – Di George syndrome

Di George syndrome results from a heterozygous deletion on chromosome 22.  Affected individuals have cardiac abnormalities, parathyroid dysfunction and thymic hypoplasia.

Defective development of the thymus leads to reduced T-cell numbers and immunodeficiency.

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