Normal adaptive immunosurveillance is the domain of T cells.
T Cells are born in the bone marrow, and undergo T cell receptor (TCR) gene rearrangements in the thymus and eventually emerge as mature T lymphocytes.
There is a wide spectrum of activity of T cells, which can be divided into many sub types of cells including: T-helper (TH), natural killer (NK) cells, suppressor T cells, cytotoxic T cells, memory T cells, regulatory T cells (Tregs) and gamma delta T cells.
All T cells derive from progenitor cells in the bone marrow, which become committed to their lineage in the thymus.
All T cells begin as CD4-CD8-TCR- cells.
Recognizes antigenic peptides bound to major histocompatibility complex (MHC) molecules on the surface of antigen presenting cells (APCs) using their T-cell receptor.
Each of these subtype cells secretes a different spectrum of cytokines that play a role in signaling other cells in the immune system.
In addition, select subsets of these cells, such as the CD4‐positive Th cells, for example, can be further subdivided into discrete CD4‐positive
Subsets of T cells, such as CD4 positive TH cells can be subdivided into discrete CD4 positive Th cells with unique phenotypes including Th1, Th2 and Th17 cells.
Process of differentiation begins when tem cells migrate from the bone marrow to the thymus.
In the thymus the progenitor stem cell converts to a thymocyte with a pre-T-cell receptor complex.
The pre-T-cell complex consists of a pre-T-cell-receptor dimer and four polypeptide chains which facilitate expression of the complex on cell surface and transmit intracellular signals needed for progression of the cell to a thymocyte with expression of a mature T-cell-receptor complex with coreceptors CD4 and CD8.
T cell activation involves an initial signal which is the binding of the T cell receptor to a peptide presented by the major histocompatibility complex (MHC) on the antigen presenting cell (APC), and a second signal involving a costimulatory receptor (CD28) on the T cell surface with B7 a costimulatory ligand on the antigen presenting cell.
For a T cell to be activated and produce an immune response, an antigen-presenting cell must present two signals to the T cell: One of those signals is the major histocompatibility complex (MHC), combined with the antigen, and the other signal is the CD80 or CD86 molecule (also known as B7-1 and B7-2).
For T cells to be activated and attack an antigen, that antigen must be presented to the T cell by an antigen-presenting cell (APC).
Such activation requires two signals,one of which is called co-stimulatory signal or signal 2.
For signal 1, the APC must bind the antigen to a major histocompatibility complex (MHC) molecule, bring that complex to its surface, and present it to the T cell receptor on the surface of the T cell.
For signal 2, the APC must present a B7 protein on its cell surface to a CD28 protein on the surface of the T cell.
These two signals activate the T cell.
Without signal 2, the T cell will not be activated, and will become anergic.
T lymphocytes are activated by engagement of the T cell receptor with processed antigen fragments presented by professional antigen presenting cells, that is, macrophages, dendritic cells and B cells via the MHC.
T cells undergo differentiation, proliferation or death through the interaction of the T-cell antigen-receptor (TCR) with antigenic peptide bound to major histocompatibility complex (MHC). This process is critically regulated by the formation of immunological synapses, which are large-scale molecular movements that are accompanied by remodeling of the actin cytoskeleton.
Optimal T-cell activation requires signal 1 the recognition of the cognate peptide major histocompatibility complex (MHC) by a specific T-cell receptor and signal 2, which is ligation of the CD28 costimulatory receptor by its ligand B7.1/B7.2 (CD80/CD86).
The costimulatory molecules stabilize and propagate immunity by promoting T cell activation and proliferation.
Failure of the costimulatory signal can result in anergy.
Lymphocytes transfused with hematopoietic precursors responsible for graft-versus-host reactions as well as the graft-versus-leukemia effect.
Mounts a specific T cell response against tumor associated antigens but are unable to control tumor growth because functional impairment of such cells in the tumor’s microenvironment.
Responds to a variety of antigens with unique receptors.
Neoplasms of T-cell origin can originate from precursor thymic T lymphocytes-lymphoblastic leukemia/lymphoma or from peripheral post-thymic T lymphocytes.
CD4 is a marker for helper T cells.
CD8 is a marker for cytotoxic T cells, and is also expressed by suppressor or regulatory T cells.
The most common T-cell marker is CD3, a pan T-cell marker because it is generally present in all types of T cells.
Other subset T cell markers are CD2, CD5 and CD7 which are expressed by nonmalignant T cells.
Normal T cells express CD3, CD2, CD5, and CD7.
Normal mature T-cells express either CD4 or CD8, but not both together.
If mature T cells express both CD4 and CD8 they are to be considered abnormal cells.
PTCL-NOS is a diagnosis of exclusion.
CD30 is expressed in anaplastic large cell lymphomas.
The combination of CD10, BCL6, PD-1, and CXCL13 0.2 the diagnosis of angioimmunoblastic lymphoma.
The most common genomic abnormality in T-cell lymphomas is the loss of some T cell markers most commonly CD7, followed by CD5 and in CD2.
Patients with T-cell lymphomas and who are positive for Epstein-Barr virus have a worse prognosis, particularly him on the elderly.
High proliferative rates and elevated Ki-67 scores are associated with adverse prognosis.
Most T-cell lymphomas have clonal T-cell receptor gene rearrangements.
CD4 CD25,Foxp3 regulatory T lymphocytes comprise 5-10% of circulating CD4 positive T cells and migrate to inflammatory sites to control inmate and adaptive immune responses, especially those due to effective lymphocytes of helper T (Th) subsets : Th1, Th2, Th17, and follicular Th cells.
T regulatory cells(Tregs) play a critical role in the prevention of autoimmune disease and also a central role in the establishment and maintenance of immune tolerance after allogeneic hematopoietic stem cell transplant.
CTLA-4 (CD152) is a member of the immunoglobulin super family and is in the T-cell cytoplasm, and is expressed in CD4 + and CD8+ T cells and regulatory T cells.
After T cell activation, within 48 to 72 hours the CTLA-4 migrates to the surface of the T cell.
CTLA-4 has a higher affinity for B7 then for CD 28 and binds to it preferentially: binding of CTLA-4 to B7 results in an inhibitory signal to the T cell and down regulates the immune response.
Impairment of the expression of CTLA-4 can result in an autoimmune disease.
Polymorphisms and mutations in the CTLA-4 gene have been associated with insulin dependent diabetes, Graves’ disease, Hashimoto’s thyroiditis, systemic lupus erythematosis, and celiac disease.