Effector T Lymphocytes

Introduction

T lymphocytes arise in the bone marrow. Unlike B cells, which mature within the bone marrow, T cells migrate to the thymus gland to mature. During its maturation within the thymus, the T cell comes to express a unique antigen-binding molecule, called the T-cell receptor, on its membrane. T cell recognize antigen via these receptors (surface antigen). T-cell receptors can recognize only antigen that is bound to cell-membrane proteins called major histocompatibility complex (MHC) molecules. T cells are specific, and can able to recognize self/non-self.  These cells are responsible for cell mediated immunity of the adaptive immune system & are mainly concern with cellular immune response to intracellular pathogens such as virus and also with regulation of B cell response.

The three types of effector T cells—CD4+, T_H1 and T_H2 cells, and CD8+ CTLs—exhibit several properties.

      One group interact with mononuclear phagocytes and help them to destroy intracellular pathogens, these are called type I helper T cells or T_H1 cells.

      Another group interact with B cells and help them to divide, differentiate and make antibody, these cells are called type II helper cells or T_H2 cells.

      A third group of T cells is responsible for the destruction of host cells that have becomes infected by virus or other intracellular pathogens, this kind of action is called cytotoxicity & the cells thus called cytotoxic T lymphoid or T_C cells.

T helper and T cytotoxic cells can be distinguished from one another by the presence of either (cluster of differentiation) CD4 or CD8 membrane glycoproteins on their surfaces. T cells displaying CD4 generally function as T_H cells, whereas those displaying CD8 generally function as T_C cells.

Activation of T_C cells, which is generally similar to T_H-cell activation is initiated by interaction of the TCR-CD3 complex with a processed antigenic peptide bound to a class II MHC molecule on the surface of an antigen-presenting cell. This interaction and the resulting activating signals also involve various accessory membrane molecules on the T_H cell and the antigen-presenting cell. Interaction of a T_H cell with antigen initiates a cascade of biochemical events that induces the resting T_H cell to enter the cell cycle, proliferating and differentiating into memory cells or effector cells. Many of the gene products that appear upon interaction with antigen can be grouped into one of three categories depending on how early they can be detected after antigen recognition

      Immediate genes, expressed within half an hour of antigen recognition, encode a number of transcription factors, including c-Fos, c-Myc, c-Jun, NFAT, and NF-_B

      Early genes, expressed within 1–2 h of antigen recognition, encode IL-2, IL-2R (IL-2 receptor), IL-3, IL-6, IFN-_, and numerous other proteins

      Late genes, expressed more than 2 days after antigen recognition, encode various adhesion molecules

These profound changes are the result of signal-transduction Pathways.

T cells, NK cells, and macrophages are the most important sources of the cytokines that organize and support cell-mediated immunity.

Under the influence of T_H-derived cytokines, a T_C cell that recognizes an antigen–MHC class I molecule complex proliferates and differentiates into an effector cell called a cytotoxic

T lymphocyte (CTL). In contrast to the T_C cell, the CTL generally does not secrete many cytokines and instead exhibits cell-killing or cytotoxic activity. The CTL has a vital function in monitoring the cells of the body and eliminating any that display antigen, such as virus-infected cells, tumor cells, and cells of a foreign tissue graft. Cells that display foreign antigen complexed with a class I MHC molecule are called altered self-cells; these are targets of CTLs.

The CTL-mediated immune response can be divided into two phases, reflecting different aspects of the response. The first phase activates and differentiates naive T_C cells into functional effector CTLs. In the second phase, effector CTLs recognize antigen–class I MHC complexes on specific target cells, which leads them to destroy the target cells.

Naive TC cells are incapable of killing target cells and are therefore referred to as CTL precursors (CTL-Ps) to denote their functionally immature state. Only after a cytotoxic T lymphocytes precursor has been activated will the cell differentiate into a functional CTL with cytotoxic activity. Generation of CTLs from CTL-Ps appears to require at least three sequential signals:

      An antigen-specific signal 1 transmitted by the TCR complex upon recognition of a peptide–class I MHC molecule complex.

      A co-stimulatory signal transmitted by the CD28-B7 interaction of the cytotoxic T cell and the antigen-presenting cell

      A signal induced by the interaction of IL-2 with the high-affinity IL-2 receptor, resulting in proliferation and differentiation of the antigen-activated CTL-P into effector CTLs.

Inactivated CTL-Ps do not express (IL-2) interlukin-2 or interlukin-2 receptors. In general, though, most activated CTL-Ps require additional IL-2 produced by proliferating T_H1 cells to proliferate and differentiate into effector CTLs. The fact that the IL-2 receptor is not expressed until after a CTL-P has been activated by antigen plus a class I MHC molecule favors the clonal expansion and acquisition of cytotoxicity by only the antigen-specific CTL-Ps.

After clearance of antigen, the level of IL-2 declines, which induces T_H1 cells and CTLs to undergo programmed cell death by apoptosis. In this way, the immune response is rapidly terminated, lessening the likelihood of nonspecific tissue damage from the inflammatory response.

The role of T_H1 cells in the generation of CTLs from naïve CTL-Ps is not completely understood, and it is unlikely that a T_H1 cell and CTL-P interact directly. However, IL-2 and co-stimulation are important in the transformation of naïve CTL-Ps into effector cells, the interaction of helper T cells with antigen presenting cells can result in production of IL-2, and hence TH1 cells can be mediators in the provision of these essential requirements.

Abstract

Through all above knowledge, we get to know that effector T cells include t helper & T cytotoxic cells. And these cells are derived through T lymphocytes.

T lymphocytes are adaptive immune cells that take essential part in cell-mediated immunity.  These cells are specific & can recognize self & non self cells or organ. They possess receptors on their surface that make them unique from other lymphocytes or cells. And receptors require MHC molecule to bind.

T cells are sub-populated into different cells on the basis of their function & surface receptors.

Out of these population of T cells, effector T cells are thee i.e. type I T helper cells, type II T helper cells and T cytotoxic cells. Basically T_H1 & T_H2  are sub-division of T helper cells.

T helper cells and T cytotoxic cells differentiate because of cluster of differentiation (CD4 for T_H & CD8 for T_C cells) & their surface receptors.

When a foreign antigen comes in our body with MHC molecule on its surface, then effectors T cells got activate. Firstly T_H cell receptors bind with MHC class II molecule & become effector cell, and thus activate T cytotoxic cells & other important cells that take part in immune response. In its result a gene product is formed that categorized according to their mode of antigen reorganization i.e. intermediate, early and late genes.

Thus activated cytotoxic T lymphocytes, from T helper cells, undergo two different phases. In its first phase it differentiate effector T cells from naïve T cells and in second stage they binds with MHC class II molecule with the help of TCRs & destroy cell by releasing cytokines.

Naive cytokines cannot kill targeted cell, thus referred as cytotoxic T precursors. While these precursors activate cytotoxic T cells by getting three different signals. First when an antigen recognize class I MHC molecule complex, second signal is transmitted by interaction of CTLs and APCs & last signal is induced by interlukin-2 that help in differentiation of antigen-activated CTL-P into effector CTLs.

Hence after all such effects of effector T cells, antigen is degraded, the interlukin-2 level is decline and this induce T_H1 cells and CTLs to initiate the process of apoptosis.

References

Books

      Basic Immunology by Abdul K. Abbas, Andrew H. Lichtman (3^rd edition).

       Cellular & molecular immunology By Abdul K. Abbas, Andrew H. Lichtman & Shiv Pillai     (6^th edition).

      Immunology by David Males, Jonathan Brostoff, David B Roth & Ivan Roitt (7^th edition).

      Immunology by Kuby (6^th edition).

Websites

      Wikipedia.