|Index to this page|
These cells have a number of direct functions, but they get their name from the help they provide to other types of effector cells, such as B cells and cytotoxic T lymphocytes (CTLs). The help consists of secreted cytokines that stimulate the helped cells.
|Link to drawing showing the anatomy of the lymphatic system, including the location of the thymus (52K).|
|Discussion of how antigens are presented to T cells|
|More on dendritic cells.|
The paracrine stimulation by these cytokines causes the Th1 cells to secrete their own lymphokines:
Th2 cells are produced when antigen-presenting cells (APCs) present antigen (e.g., allergens) to the T cell's receptor for antigen (TCR) along with
The identity of the APCs for Th2 responses is still uncertain. Some research indicates that basophils are the APCs, but other research questions this role.The major lymphokines secreted by Th2 cells are
|Link to graphic showing how Th2 cells stimulate B cells to mature into antibody-secreting plasma cells.|
|Two transcription factors have been found that play a critical role in the choice between becoming a Th1 or a Th2 cell.
GATA3 produces Th2 cells by
The antigenic stimulus that sends pre-Th cells down one path or the other also sets the stage for reinforcing the response.A Th1 response inhibits the Th2 path in two ways:
Chemokines are cytokines that are chemotactic for (attract) leukocytes. The members of one group, who share a pair of adjacent cysteine (C) residues near their N-terminal, are designated CC chemokines.
Chemokines bind to receptors on the responding leukocyte. The receptors are transmembrane proteins with the chemokine binding site exposed at the surface of the plasma membrane. CC chemokine receptors are designated CCR.
With their different functions, we might expect that Th1 cells and Th2 cells would respond differently to chemokines. And so they do.
One chemokine that binds to CCR3 is called eotaxin. It is secreted by epithelial cells and phagocytic cells in regions where allergic reactions are occurring.CCR3 is found on
|One striking illustration: an AIDS patient with leukemia was given a bone marrow transplant from a donor whose cells expressed a nonfunctional version of CCR5. Two years later, the patient was not only cured of his leukemia but of AIDS as well.|
|Another: Gene therapy in which samples of a patient's CD4+ T cells were treated in vitro so that their CCR5 gene became nonfunctional [how it was done]. Expanded in culture and then returned to the donor, five (of six) patients had their CD4+ T cell counts rebound.|
Tfh cells are a recently-identified subset of CD4+ helper T cells. They are found in nests of B cells — called follicles — in the lymph nodes.They probably start out like other "naive" Th cells, but when exposed to
Th17 cells are another recently-identified subset of CD4+ T helper cells. They are found at the interfaces between the external environment and the internal environment, e.g., skin and lining of the GI tract.They probably start out like other "naive" Th cells, but when exposed to
Situated in the skin and the lining of the GI tract, Th17 cells are positioned to attack fungi and bacteria at those locations. They do this by secreting defensins and recruiting scavenging cells, especially neutrophils, to the site. The result: clearing away of the invaders with accompanying inflammation.But inflammation is a double-edged sword. So it is not surprising that Th17 cells have been implicated as potent effectors of such autoimmune disorders as
|Effector Cytokine(s)||Main Target Cells||Effector Functions||Pathological Effects|
|Th1||IL-12||T-bet||IFN-γ & IL-2||Macrophages, dendritic cells||Intracellular pathogens||Autoimmunity;
|Th2||IL-4||GATA3||IL-4, IL-5 & IL-13||Eosinophils, basophils, B cells||Extracellular pathogens||Asthma and IgE-mediated allergies|
|Tfh||IL-6 & IL-21||Bcl6||IL-21||B cells||Class Switch Recombination and Affinity Maturation of antibodies||Autoimmune diseases?|
Inhibited by retinoic acid
|RORγt||IL-17 & IL-22||Neutrophils||Extracellular bacteria;
Stimulated by retinoic acid and IL-2
|Foxp3||IL-10 & TGF-β||all the other types of T cells||Immunosuppression; anti-inflammatory||None?|