Stem Cell Factor (c-kit Ligand)

 Stem cell factor is a cytokine that interacts with a tyrosine kinase membrane receptor, the protein product of the cellular oncogene c-kit. The cytokine that interacts with this receptor is called c-kit ligand, or stem cell factor, because it acts on immature stem cells.

Stem cell factor is needed to make bone marrow stem cells responsive to other CSFs but it does not cause colony formation itself. Stem cell factor may also play a role in sustaining the viability and proliferative capacity of immature T cells in the thymus and mast cells in mucosal tissues.

Colony-Stimulating Factors

A variety of CSFs, such as granulocyte-CSF (G-CSF) and GM-CSF, are also made by T cells. These pathways provide a link between the lymphoid and hematopoietic systems. For example, G-CSF and GM-CSF regulate the production of granulocytes and monocytes, thus enabling the T cell system to promote the inflammatory response.

The biological activity of CSF is measured by its ability to stimulate hematopoietic progenitor cells to form colonies in semisolid medium. These proteins are necessary for the survival, proliferation, and differentiation of precursor cells of the immune system.

CSFs are potentially important in the treatment of human disease. GM-CSF has been used in a number of clinical trials to increase circulating leukocytes in patients with AIDS, other immunocompromised patients (e.g., those recovering from chemotherapy), and bone marrow transplant recipients.

Transforming Growth Factors

As with the IFNs, transforming growth factors (TGFs) were identified as products of virally transformed cells. These factors were found to induce phenotypic transformation in non- neoplastic cells and subsequently were termed transforming growth factors. TGF-β is a group of five cytokines released by many cell types, including macrophages and platelets. TGF-β is known to be a potent inhibitor of IL-1–induced T cell proliferation.

The principal action of TGF-β in the immune system is to inhibit the proliferation and activation of lymphocytes and other leukocytes. It inhibits the proliferation and differentiation of T cells and the activation of macrophages.

Chemokines

 Chemokines are a large family of structurally homologous cytokines that stimulate transendothelial leukocyte movement from the blood to the tissue site of infection and regulate the migration of polymorphonuclear leukocytes (PMNs) and mononuclear leukocytes within tissues. The largest family consists of CC chemokines that attract mononuclear cells to sites of chronic inflammation, such as monocyte chemoattractant protein 1 (MCP-1). A second family of chemokines consists of CXC chemokines, of which IL-8 (CXCL8) is the prototype. CXCL8 attracts PMNs to sites of acute inflammation, activates monocytes, and may direct the recruitment of these cells to vascular lesions. The third family, CX3, forms a cell adhesion receptor capable of arresting cells under physiologic flow conditions. TNF-α–converting enzyme can cleave CX3CL1 from the cell membrane.

Other functions of various chemokines include the following:

• Increasing the affinity of leukocyte integrins for their ligands on endothelium (e.g., intercellular adhesion molecule-1 [ICAM-1], ICAM-2, vascular cell adhesion molecule-1 [VCAM-1])

• Regulating the traffic of lymphocytes and other leukocytes through peripheral lymphoid tissues

 • Maintaining normal migration of immune cells into lymphoid organs or other specialized cells to particular sites

Assessment of Cytokines

 Defects in cytokine production can lead to autoimmunity (Table 1). Traditional methods for assessment of cytokines include the following:

 • Bioassays

• Enzyme-linked immunosorbent assay (ELISA)

• Intracellular staining

• Ribonuclease protection assay

• Polymerase chain reaction (PCR)

Table1. Defects in Cytokine Production that Can Lead to Autoimmunity

Newer methods of measurement include the following:

• Multiplexed assay using the FlowMetrix; quantifies multiple cytokines simultaneously

• Intracellular staining using flow cytometry

 • Cord blood mononuclear cells stimulated by allergens (celELISA).

• Real-time PCR for lymph nodes or spleen

 • Enzyme-linked immunosorbent spot (ELISPOT) assays

• Enhanced immunoassays for cytokines

 • Biotrak assay—high-sensitivity ELISA

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مواضيع ذات صلة

The Complement System: Diagnostic Evaluation

Biological Functions of Complement Proteins

The Complement System: Alternative Pathway

The Complement System: Classic Pathway

The Complement System

Immune-Mediated Disease

Evaluation of Immunodeficiency Syndromes

Plasma Cell Biology

B Lymphocyte Subsets

Natural Killer and K-Type Lymphocytes

Antigen Recognition by T Cells

Antigen Processing and Antigen Presentation to T Cells