T helper cell
Genetic variation in regulatory elements expressed by CD4+ cells determines susceptibility to a broad class of autoimmune diseases.
These are defined by the presence of a lineage-determining (or lineage-specifying) transcription factor (also called master regulator, though the term has been criticized for being too reductive).
[2] The loss of function in a lineage specifying transcription factor results in the absence of the corresponding class of helper T cell which can be devastating for the health of the host.
Of note, only a very small minority of T cells egresses from the thymus (estimates commonly range from 1–5% but some experts feel even this is generous).
[3] Maturation of RTE in SLO results in the generation of mature naive T cells (naïve meaning they have never been exposed to the antigen that they are programmed to respond to), but naive T cells now lack or have downregulated (reduced) expression of the RTE-related surface markers, such as CD31, PTK7, Complement Receptor 1 and 2 (CR1, CR2) and the production of interleukin 8 (IL-8).
Class II MHC proteins are generally only found on the surface of professional antigen-presenting cells (APCs).
MHC Class II binding pockets are flexible with respect to the length of the peptides they hold.
[10] During an immune response, professional antigen-presenting cells (APCs) endocytose antigens (typically bacteria or viruses), which undergo processing, then travel from the infection site to the lymph nodes.
[12] Once at the lymph nodes, the APCs begin to present antigen peptides that are bound to Class II MHC, allowing CD4+ T cells that express the specific TCRs against the peptide/MHC complex to activate.
When these all come together, the CD4 is able to recruit a kinase called Lck which phosphorylates immunoreceptor tyrosine-based activation motifs (ITAMs) present on the CD3 gamma, delta, epsilon, and zeta chains.
The loss of CD45 produces a form of SCID because failure to activate Lck prevents appropriate T cell signaling.
It achieves this by releasing a potent T cell growth factor called interleukin 2 (IL-2) which acts upon itself in an autocrine fashion.
[citation needed] The autocrine or paracrine secretion of IL-2 can bind to that same Th cell or neighboring Th's via the IL-2R thus driving proliferation and clonal expansion.
[citation needed] In 1991, three groups reported discovering CD154, which is the molecular basis of T cell helper function.
[17] Randolph Noelle at Dartmouth Medical School generated an antibody that bound a 39 kDa protein on murine T cells and inhibited helper function.
In order to be effective, helper T cells must determine which cytokines will allow the immune system to be most useful or beneficial for the host.
Understanding exactly how helper T cells respond to immune challenges is currently of major interest in immunology, because such knowledge may be very useful in the treatment of disease and in increasing the effectiveness of vaccination.
IFN-γ secreted by CD4 T cells can activate macrophages to phagocytose and digest intracellular bacteria and protozoa.
[20] Th2 helper cells lead to a humoral immune response,[19] typically against extracellular parasites such as helminths.
Various evidence suggests that the type of APC presenting the antigen to the T cell has a major influence on its profile.
Other evidence suggests that the concentration of antigen presented to the T cell during primary activation influences its choice.
[26] This means that Th17 cells are especially good at fighting extracellular pathogens[26] and fungi, particularly during mucocutaneous immunity against Candida spp.
As such, hIL-10 is not believed to truly promote the Th2 response in humans, but acts to prevent over-stimulation of helper T cells while still maximising the production of antibodies.
These IL-17 producing cells were initially described as a pathogenic population implicated in autoimmunity but are now thought to have their own distinct effector and regulatory functions.
[32] That said, the Th model has still played an important part in developing our understanding of the roles and behaviour of helper T cells and the cytokines they produce during an immune response.
[citation needed] This is initially compensated for via the production of new helper T cells from the thymus (originally from the bone marrow).
Studies suggest that only ~5% of the lymphoid-derived CD4 T cells targeted by HIV are permissive and become productively infected with the virus.
The depletion of CD4 T cells and the development of chronic inflammation are signature processes in HIV pathogenesis that propel progression to acquired immune deficiency syndrome (AIDS).
Two components of the immune system are particularly affected in AIDS, due to its CD4+ T cell dependency: If the patient does not respond to (or does not receive) HIV treatment they will succumb usually to either cancers or infections; the immune system finally reaches a point where it is no longer coordinated or stimulated enough to deal with the disease.
Triggering PD-1 expressed on activated monocytes by its ligand PD-L1, induces IL-10 production which inhibits CD4 T-cell function.
