Interferon -y secretion

Tang MLK, Kemp AS, Thorburn J, Hill DJ Reduced interferon-y secretion in neonates and subsequent atopy. Lancet 1994 344 983-986. 

Although this may suffice, additional factors contribute to this process. Activated T-lymphocytes secrete amongst other cytokines also interferon y which... 

For the pathogenesis of multiple sklerosis, autoimmune T-lymphocy tes play a predominant role, which are directed against components of the neural myelin sheath. T-lymphocy tes by secreting cytokines such as interferon y maintain the chronic inflammation which destructs the myelin sheath. Also cytotoxic T-lymphocytes may participate directly. The cause of multiple sklerosis is unknown. Significantly increased antibody titers against several vitusses, mostly the measles virus, point to a (latent) virus infection initiating the disease. 

Kumar, V., Bhardwaj, V., Soares, L., Alexander, J., Sette, A. and Sercaz, E. (1995) Major histocompatibility complex binding affinity of an antigenic determinant is crucial for the differential secretion of interleukin 4/5 or interferon-y by T cells. Proceedings of the National Academy of Sciences USA 92, 9510-9514. 

Successful containment of M. tuberculosis requires activation of a subset of CD4 lymphocytes, referred to as Th-1 cells, which activate macrophages through secretion of interferon y. 

Figure 3 Cytokine secretion in immunopotentiating reconstituted influenza viro-somes (IRIV)-stimulated peripheral blood mononuclear cells (PBMC). PBMC from a healthy donor were cultured in the absence of stimuli (Neg) or in the presence of IRIV (V, 1 50 diluted) or control liposomes (L, 1 50 diluted). On days 1, 2, and 4 supernatants were harvested and the concentrations of interferon-y (A), GM-CSF (B), TNF-a (C), and interleukin-4 (D) were determined by ELISA. Abbreviations GM-CSF, granulocyte monocyte colony stimulating factor TNF-a, tumor necrosis factor-a. Source From Ref. 6.

Interferons are natural proteins produced by the cells of the immune system in response to challenges by foreign agents such as viruses, parasites and tumor cells. Interferons assist the immune response by inhibiting viral replication within host cells. There are three major classes of interferons, interferon type I, interferon type II and interferon type III. They bind to a differen cell surface receptor complexes. The type I interferons in humans are IFN-o , IFN-jS and IFN- >. IFN-y is human interferon type II. All classes of interferon are important in fighting RNA virus infections and endogenous interferons are secreted when abnormally large amounts of dsRNA are found in a cell. 

Cytokines, including tumour necrosis factor (TNF) and interferon-y, favour the secretion of numerous chemokines and the expression of adhesion molecules by endothelial cells. The mechanisms of action of the principle drugs used in MS, and in priority beta interferons, are the following (1) inhibition of the expression of major histocompatibility complex class II molecules, (2) inhibition of metal-loproteases, (3) induction of immunosuppressor cytokines. 

Specific cellular immunity is a type of (more specialized) acquired immunity which is based primarily on T lymphocytes. Several subpopulations of T lymphocytes are differentiated in the thymus, where one subset has identical structures on the cell surface to recognize a specific set of antigen. Each subpopulation performs different effector functions. The dominant T-cell type involved is the so-called cytotoxic T lymphocyte. In addition, T-helper cells are important for enhancing the immune response. By synthesizing and secreting various cytokines such as interferon y (INF-y or interleukin 2 (IL-2), T-lymphocytes also have an important role in controlling other major parts of the immune system. 

Although T cells can be divided into two populations (helper/inducer and cytotoxic/suppressor) based on CD4 and CD8 expression, T cells can also be divided into two populations based on the structure of the antigen receptor complex, either alp, or yIS, associated with the CD3 antigen (DIO). The yIS T cells represent approximately 5% of all T cells, lack expression of CD5, CD4, and often CD8, are thought to be associated with a more primitive type of immune response, and are usually found in the splenic red pulp and epithelial sites (A15, C26, T6). The alj3 T cells usually express all four pan-T cell antigens (CD2, CD3, CD5, and CD7) and either CD4 or CD8. The CD4-positive cells can be further divided based on cytokine secretion Thl cells, which secrete interleukin-2 (IL-2) and interferon y and help macrophages and other T cells, and Th2 cells, which secrete IL-4, IL-5, IL-6, and IL-10 and help B cells in antibody production (DIO, Dll). 

Cause increased activity of phagocytes and lymphocytes, cause increased secretion of certain cytokines interferon-y (IFN-y), IL-2, and IL12, which are critical for differentiation of ThO cells toward Thl line... 

Klinman DM, AE-Kyung Y, Beaucage SL, Conover J, Krieg AM. CpG motifs present in bacterial DNA rapidly induce lymphocytes to secrete interleukin 6, interleukin 12, and interferon y. Proc Nat Acad Sci USA 1996 93 2879-83. 

After binding and phagocytosis, alveolar macrophages and monocytes release pro-inflammatory cytokines, e.g. lL-1, interferon-y and tumor necrosis factor-a (fig. 1). These cytokines activate resident cells (epithelial cells, fibroblasts) to produce chemokines such as lL-8, granulocyte-monocyte-colony-stimulating factor, RANTES (regulated on activation normal T cell expressed and secreted) that will result in a second wave of cell recruitment (mononuclear and polymorphonuclear cells). 

The balance between the levels of Thl and Th2 cytokine levels secreted may be crucial to attaining therapeutic efficacy of the immunostimulant because Thl and Th2 have opposing actions (184). For example, a glycolipid agonist that stimulates NKT cells to produce Thl-type cytokines (such as interferon-y and the interleukins IL-2 and IF-12) would be beneficial for... 

Maes M, Schai pe S, Meltzer HY, Okayli G, Bosnians E, D Hondt P, Van den Bossche BV, Cosyns P (1994) hicreased neopterin and interferon-gamma secretion and lower availability of L-ti yptophan in major depression Eui tlier evidence for an immune response. Psycliiati y Res 54 143-160. 

In the 1980s, studies with EAE, an animal model mimicking MS, indicated that interferon y (IFN y) was effective in treating that disease and a trial was initiated to evaluate its potential benefit in human MS. Rather than showing efficacy, in 1987, use of IFNy as a therapy in MS patients caused an increase in clinical exacerbations and forced the clinical trial to terminate early (Panitch et al., 1987). Associated study of IFNy in 20 MS patients indicates increased concentrations of IFNy and TNFa precede the observation of clinical defects (Beck et al., 1988). An evaluation of primary RR-MS patient lymphocytes using flow cytometry supports a correlation between EDSS scores and IFNy secretion (Petereit et al, 2000). Intracellular cytokine immuno-staining of anti CD8-I- T cells reveals a correlation with IFNy and disease phase but not disease activity (Becher et al., 1999). What initially seemed efficacious in the EAE animal model, not only did not decrease MS symptoms but is now felt to be a marker of active inflammatory disease. 

In recent years it has become clear that the nature of the immune response initiated by CD4 T lymphocytes is at least partly dependent on the selection or preferential activation of particular subsets of CD4 T lymphocytes which secrete defined patterns of cytokines (Table 2.3). These patterns of cytokine release result in the initiation and propagation of distinct immune effector mechanisms. Initial studies of mouse CD4 T lymphocyte clones revealed that these could be divided into two basic fiinaional subsets termed ThI and Th2. ThI T lymphocytes were characterized by the predominant secretion of IL-2, interferon y (IFNy) and tumour necrosis factor 8 (TNF/3), while Th2 cells characteristically... 

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