T helper cell
T helper cells (abbreviated to T H cells ) are a group of T lymphocytes in the blood that have a helper function. Based on the cytokines they release, they are divided into two important subgroups (subpopulations) that have different functions. One subgroup (called type 1 T helper cells) is involved in the cellular immune response , while the other subgroup (called type 2 T helper cells) is involved in the humoral immune response . Another type of T helper cell was discovered in 2005. This type forms u. a. IL-17 and therefore plays a role in regulating inflammatory processes.
General characterization of the T helper cells
The functionally opposing division (dichotomy) into type 1 and type 2 T cells has been described as an example for CD4- positive lymphocytes, but also applies to CD8 -positive T cells and cells with a γδ T cell antigen receptor. Type 1 T cells are determined to be CD4-positive and CD8-positive lymphocytes, which typically secrete interferon -γ (IFN-γ), IL-2 and TNF-α . Correspondingly, CD4-positive or CD8-positive lymphocytes, which have the typical cell property that releases the cytokines IL-4 , IL-5 , IL-6 , IL-10 and IL-13 , are referred to as type 2 T cells.
This classification is a simplified consideration due to the extreme reaction possibilities of the cytokine-secreting T cells. T cells are found in both tissue and peripheral blood with a cytokine pattern that is typical of both type 1 and type 2 T cells. These cells are sometimes referred to as Type0 T cells.
The differences between type 1 T cells and type 2 T cells were first described in 1986 by Tim Mosmann and Robert L. Coffman .
Type 1 T helper cells (T H 1 lymphocytes)
The cell-mediated defense of the acquired immune system takes place mainly using activated T lymphocytes and macrophages . Certain antigens cause the activation, accelerated proliferation and differentiation of T cells with specificity for these antigens. Activated type 1 T cells are characterized by the release of cytokines such as IFN-γ , IL-2 and TNF-α , which activate and differentiate macrophages.
The macrophages in turn promote the type 1 polarization of reactive T cells through their cytokine release (IL-12). At the same time, the macrophages intensify their effect as antigen presenting cells (APC) and improve their antimicrobial ability to act against extra- and intracellular antigens . The co-stimulating surface molecules CD40 , CD80 and CD86 and the MHCII molecules are upregulated . As a result, MHC production and peptide processing (i.e. overall peptide presentation) increase.
The T-cell-mediated inflammatory reaction increases the blood flow via the expansion of the local vessels ( vasodilation ). The upregulation of adhesion molecules on endothelial cells leads to an increased migration of further cells from the peripheral blood into the tissue . Finally, fibrin is formed as a local anti-inflammatory factor . CD8-positive T cells are also involved in inhibiting the spread of disease triggers ( pathogens ). They contribute to tissue damage through their release of IFN-γ and direct cytotoxicity .
B-lymphocytes are also stimulated (but not as strongly as by type 2), namely by class change to the production of opsonizing antibodies (especially IgG ), i.e. those antibodies that can make objects eat by macrophages. At the same time, a type 2 response is inhibited by the cytokines released. Such a response is triggered by IFN-γ and IL-12, which are formed by natural killer cells ( NK cells ) and dendritic cells . This path is used in particular to combat some intracellular bacteria and viral infections . The production of IFN-γ simultaneously blocks the differentiation into type 2 cells.
In addition, type 1 cells are able to fight infections caused by bacteria that multiply in the vesicles of macrophages. Examples of this are the pathogen causing tuberculosis ( Mycobacterium tuberculosis ) and the leprosy pathogen ( Mycobacterium leprae ). The type 1 cells activate the infected macrophages and thereby trigger the fusion of the infected vesicles with lysosomes , whereby the pathogens are digested.
Type 2 T helper cells (T H 2 lymphocytes)
The most important function of the type 2 polarized CD4 positive T cells is the interaction with B lymphocytes , which takes place via cytokines and cellular molecules and leads to the production and release of antibodies. This is essential for the humoral immune response and takes place through the typical cytokine pattern of type 2 CD4 positive T cells (IL-4, IL-5, IL-6, IL-10, IL-13 and lymphotoxin-α ).
The cytokines released by type 2 T cells inhibit the mechanisms that lead to a type 1 response. This cross-inhibition maintains a direction for the immune response that has once been taken. IL-10 in particular inhibits macrophage activation. The antigen-specific help provided in the immune response of type 2 T cells not only leads to their activation, proliferation and differentiation in B cells , but also stimulates mast cells as well as basophilic and eosinophilic granulocytes . IL-4 has a special function within the series of cytokines that stimulate the secretion of immunoglobulins. In the context of the activation and differentiation of B cells, it is primarily responsible for the formation of neutralizing antibody classes, i.e. for a class change (English isotype switch ) to IgA , IgG, IgE . Type 2 T cells can stimulate B cells very strongly. The humoral immune response is mainly triggered by the cytokine IL-4, IL-6 intensifies this tendency. IL-4 inhibits the activation of macrophages. IL-10 reduces the production of IFN-γ in T cells and macrophages.
Type 17 T helper cells (T H 17 lymphocytes)
T H 17 lymphocytes seem to play an important role in regulating inflammatory processes. It is interleukin-6 is a necessary signal which is the conversion of a naïve CD4 + T-cell into a T H coordinated 17 cell. The role of T H 17 lymphocytes has not yet been conclusively clarified and is the subject of current research.
Antigen recognition of CD4-positive T cells
In their function as antigen-presenting cells , B cells, dendritic cells or macrophages can recognize and absorb antigens on the basis of specific epitopes . The antigen is processed inside the cell and presented to CD4-positive T cells in the form of smaller peptides together with MHC class II molecules.
Activated CD4 + T helper cells play a crucial role in the activation (licensing) of mature, antigen-presenting dendritic cells. The help of CD4 + T cells is absolutely necessary in order to generate a long-lasting, effective immune response of cytotoxic CD8 + T cells. Only when the dendritic cell interacts with the T helper cell and the CD8 + T cell at the same time is an effective, secondary expansion of the cytotoxic T cells possible.
literature
- Georg Andreas Peter Holländer: Immunology, basics for clinics and practice . 1st edition. Elsevier, Munich 2006, ISBN 3-437-21301-6 .
- Michael John Owen, Jonathan R. Lamb: Immune recognition . Thieme, Stuttgart 1991, ISBN 3-13-754101-8 .
Individual evidence
- ^ A b Harrington, Laurie E, Robin D Hatton, Paul R Mangan, Henrietta Turner, Theresa L Murphy, Kenneth M Murphy, and Casey T Weaver .: Interleukin 17-producing CD4 + effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages . In: Nature Immunology . tape 6 , no. 11 , 2005, p. 1123-1132 , PMID 16200070 .
- ↑ Tim Mosmann, H Cherwinski, MW Bond, MA Giedlin, RL Coffman: Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins . In: The Journal of Immunology . Volume 136, No. 7 , 1986, pp. 2348-2357 ( abstract ). ISSN 0022-1767
- ↑ Immunol Res. 2009 Dec; 45 (2-3): 209-17. doi: 10.1007 / s12026-009-8102-0 . Epub 2009 Feb 18. Unraveling the mechanisms of help for CD8 + T cell responses. Livingstone AM., Et al.
- ↑ Eur J Immunol. 2014 Dec; 44 (12): 3543-59. doi: 10.1002 / eji.201444477 . Epub 2014 Oct 27. Concurrent interaction of DCs with CD4 (+) and CD8 (+) T cells improves secondary CTL expansion: It takes three to tango. Hoyer S., et al.