• The leukocyte that matures in the thymus and that brings about cell mediated immunity is called T lymphocyte. They mature in the thymus and hence the name.
• It is a type of white blood cell. They have a large nucleus and a rim of cytoplasm. They are highly concentrated in the blood and spleen.
• They are derived from the haematopoietic stem cells of bone marrow.
• They make up 77% of the lymphocytes and B cells form only 23%.
• There are 8 different types of T cells. They are:
  • T helper cells (TH cells)
  • T cytotoxic cells (TC cells) or T killer cells (TK cells)
  • T regulatory cells (TReg)
  • T delayed type hypersensitivity cells (TD cells)
  • Alpha-beta T cells Gamma-delta T cells
  • Natural killer T cells
  • Memory T cells
• T cell has the following surface markers:
  • Erythrocyte receptor (T11)
  • T cell receptor (TCR)
  • Ia protein (Immune associated)
  • IL-I and IL-2 receptors
• The surface of the T cell has T cell receptors (TCR). The TCR of TH cell and TC cell recognizes the antigen presented by the antigen presenting cells. These T cells are activated.
• The activated TH cell secretes cytokines. The cytokines activate the B cells and other types of T cells. The activated B cells bring about humoral immune response. The activated T cells bring about cell mediated immune response.

Functions of T Cells

• Bring about cell mediated immune response.
• Kill infected cells.
• Kill tumor cells.
• Reject grafTS.
• Kill bacteria and viruses hidden inside cells.
• T helper cells activate other T cells and B cells.

Types of T Cells

1. T Helper Cells (TH cells)

• T helper cells are a class of WBC.
• T helper cells are a sub population of T lymphocytes that help B cells and other T cells in immune responses. They are the regulator cells. They help the B cells and T cells in multiple ways.
• The T helper cells are represented by TH.
• The T helper cells contain glycoprotein molecules called CD4 molecules (cluster of differentiation) on the surface. Hence the T helper cells are also called CD4⁺ T cells. CD4 is an immunoglobulin. It is a surface marker. It is a surface receptor. TCR (T cell receptor) molecules are also present on the surface.
• The HIV infects mainly the T helper cells. TH cell recognizes the antigen-class II MHC complex of antigen presenting cells.

Activation of TH Cells

• The TH cells identify the antigen through the antigen presenting cells (APCS).
• The APCs swallow the antigen (pathogen) and deposit a fragment of the pathogen on their surface with class II MHC molecule.
• The antigen-class II MHC complex is recognized by the TH cell. The TCR of TH cell binds with the antigen-class II MHC complex of APC. This binding activates the TH cell. The TH cell divides and produces a clone of TH cells.
• The TH clone produces two types of cells, namely effector T cells and memory TH cells.
• The effector TH cells activate B cells, TC cells and macrophages. The B cells produce humoral immune response.
• The TC cell produces cell mediated immune response. The activated macrophages march towards the antigen and launch a war.
• The activated TH cells secrete lymphokines, such as Interleukin-2, BCSF-B cell stimulation factor, BCGF-B cell growth factor BCDF-B cell differentiation factor and MMIF-Macrophage migration inhibition factor.

• Interleukin-2 activates B cells, TC cells and TReg cells. BCSF stimulates B cells. BCGF induces proliferation of B cells. BCDF causes the differentiation of B cells.
• Macrophage migration inhibition factor causes the accumulation of macrophages around the antigen and the activation of macrophages to perform phagocytosis.

Function of TH Cells

• It plays a main role in adaptive immunity (acquired immunity).
• It brings about humeral immune response by activating B cells. It brings about cell mediated immunity by activating TC cells.
• It activates macrophages to induce phagocytosis.
• The cytokines of TH cells produce allergy reactions.
• TH cells identify the pathogens with the help of antigen presenting cells (APCS).

2. T Cytotoxic Cells (TC) or T Killer Cells (TK)

• The T killer cells are a sub population of T lymphocytes that kill microorganisms or body’s own cells. They are also called T cytotoxic cells. They are represented by TC or TK.
• The TC cells are effector T cells. They contain TCR on their surface. They contain on the surface CD8 molecules. Hence the killer cells are also called CD8⁺ T cells.
• The TCR of TC cells recognizes antigen with class I MHC molecules. The cytotoxic T cell can directly attack a cell thereby capable of killing microorganisms and body’s own cells.

Targets of TC Cells

• TC cells kill the following targets:
• Virus-infected cells
• Bacteria-infected cells
• Protozoa-infected cells
• Cancer cells
• Allograft
• Beta cells of islets of Langerhans

Mechanism of Killing

• TC cells recognize the antigen through the TCR present on their surface. TC cells recognize the antigen directly or through the antigen presenting cells (APCs).
• The APC deposits a fragment the pathogen on Class I MHC. This antigen – Class I MHC complex is recognized by the TCR of TC cell. This binding activates the TC cell.
• The TC cell is also activated by TH cells. The activated TC cell produces a clone of TC cells by mitosis.

• Most the cells of the clone become effector TC cells and a few cells become memory TC cells.
• The effector TC cells release cytotoxic substances. The cytotoxic substances include perforin, granzymes and granlysin.
• Perforin forms pores in the plasma membrane of target cell. Granzymes and granlysin enter the target cell through the pores. These enzymes cause the apoptosis (programed cell death) of the target cell.

Functions

• TC cells bring about cell mediated immunity. It is remarkable to see that each killer cell can attack many microorganisms one after another, thereby killing many, without the killer cells being harmed.
• The cytotoxic T cells (TC) are lethal to virus infected cells bacteria – infected cells and protozoa infected cells. The cytotoxic cells also play an important role in destroying cancer cells. They also kill tissues of allograft (tissue graft of foreign animals).
• They are responsible for graft rejection.
• They kill beta cells of islets of Langerhans leading to diabetes mellitus.

3. Regulatory T Cells (TReg Cells)

• Regulatory T cells (TReg cells) suppress the activities of other T cells and B cells. Formerly they were called suppressor T cells (TS cells).
• TReg cell is a subset of TH cell. They are CD4⁺ cells.
• They express a trans membrane factor called CD25; this is the alpha chain of the receptor for interleukin-2.
• They express transcription factor called Foxp³ that alters the expression of many genes.
• They express a cell surface protein called CTLA-4. (cytotoxic T-lymphocyte-associated antigen 4)
• They express αẞTCR (alpha-beta T cell receptor) for antigen.
• TReg cells are activated by two signs namely:
• Peptide-class II MHC complex
• Costimulation from B7 molecules (also known as CD80 and CD86 present on APC).
• The activated TReg cells secrete large amount of interleukin-10 and TGF-β. IL-10 is a powerful immunosuppressant. It inhibits TH 1 cells, TH 2 cells, TH 17 cells, NK cells, TC cells.
• TReg cells also kill TC cells by binding to them and secreting granozymes and perforins.
• The most important suppressor mechanism of TReg cell is the effect on APCs like dendritic cells.
• The CTLA-4 molecules on TReg cells bind tightly to the B7 molecules on the APCs, strip them off the B7, engulf them by endocytosis and destroy them.
• Having lost their B7 molecules, the APCs can no longer present costimulatory signal to activate effector T cells.
• TReg cell is activated by IL-2 and this leads to rapid proliferation. As IL-2 is secreted by T effector cells, this provides a negative feedback mechanism. Inflammatory TH cell activity is restrained by the resulting expansion of TReg cells.

TReg Subsets

• There are two subsets of TReg cells. They are: t TReg cells (Thymic TReg cells) and p TReg cells (Peripheral TReg cells).
• t TReg cells originate in the thymus. They recognize self-antigens deposited on MHC molecules. They inhibit other T cells for mounting attack against self-antigens. They protect the body against autoimmunity.
• pTReg cells develop from various tissues of the body throughout life. They originate from CD4 cells. They are abundant at mucosal surfaces that separate the external environment from the internal environment.

4. T Delayed Type Hypersensitivity Cells (To Cells)

• TD cells are a sub population of T lymphocytes that bring macrophages to areas where delayed hypersensitivity reactions occur.
• TD cells are similar TD T cells. TD cells secrete primarily macrophage chemotoxin factor and macrophage migration inhibition factor. By secreting these lymphokines the TD cells are directly involved in the delayed hypersensitivity reactions.
• Macrophage chemotoxin attracts monocytes and macrophages whereas the macrophage migration inhibition factor inhibits the migration of macrophages and monocytes thereby infiltration of these cells occur into tissues where a delayed type hypersensitivity reaction is occurring.

5. Alpha-Beta T Cells

• In alpha-beta T cells, the TCR has an alpha chain and a beta chain.

6. Gamma-Delta T Cells

• Gamma-delta T cells contain TCR which is made up of gamma chain and delta chain.
• They can bind TD intact antigens containing phosphorus atoms. They do not bind to antigens presented on MHC molecules and antigens presented by APCs.
• They do not contain CD4 and CD8 molecules.
• They develop in the thymus. After maturity, they migrate to epithelia of intestine, skin, lining of vagina, etc.
• They carry out immune surveillance.

7. Natural Killer T Cells (NKT Cells)

• Natural killer T cells are a class of T cells abbreviated as NKT cells.
• NKT cells recognize glycolipid antigens presented by a molecule called CD1d. The activated NKT cells function like TH and TC cells. They produce cytokines and cytolytic molecules.
• They also eliminate some tumor cells and cells infected with herpes virus.

8. Memory T Cells

• Memory T cells are produced by activated T cells. They remember the antigen which activated them. They mount a quick action when the same antigen infects again. They contain either CD4 or CD8.
• They express another protein on the surface called CD45 RO.