Th cell differentiation

Kelschenbach J, Barke RA, Roy S (2005) Morphine withdrawal contributes to Th cell differentiation by biasing cells toward the Th2 lineage. J Immunol 175 2655-2665. 

Ohyanagi N, Miyasaka N, Nanki T et al. 2009. Retinoid amehorates experimental autoimmune myositis, with modulation of Th cell differentiation and antibody production in vivo. Arthritis Rheum. 60 3118-27. 

Sinee the initial finding that IFN-y secretion from activated T cells can induce indirect cytotoxicity by release of reactive species (later identified as NO and per-oxynitrite) from macrophages (Nathan et al. 1983 Nathan et al. 1984) an increasing amount of data on the role of NO in the immune and inflammatory systems have accumulated. NO has been shown to influence different immune functions both during innate and adaptive immune responses, including T-ceU activation and proliferation, cytokine production, APC expansion and maturation, central and peripheral tolerance, Th cell differentiation, as well as T-ceU apoptosis (Brito et al. 1999 MacMicking et al. 1997). 

Else, KJ., Hultner, L. and Grencis, R.K. (1992) Cellular immune responses to the murine nematode parasite Trichuris muris. II. Differential induction of TH-cell subsets in resistant versus susceptible mice. Immunology 75, 232-237. 

The initial event responsible for the development of allergic diseases is the generation of allergen-specific CD4-F T-helper (Th) cells. The current view is that under the influence of IL-4, naive T cells activated by antigen-presenting cells differentiate into Th2 cells [34-36]. Once generated, effector Th2 cells produce IL-4, IL-5 and IL-13, and... 

With the foregoing assumptions, the process steps of interest may be described starting with two material balances, a balance for the light component and a total balance The balances are taken on the first and i-th cells and are written for a differential time dt. 

EAE is traditionally regarded as a prototypic TH-1 CD4+ T-cell mediated autoimmune disease of the CNS. However, other cells of the immune system play important roles in the neuropathogenesis of this disorder. Defining the precise role of various cell types in EAE is complicated by the diverse and heterogeneous nature of EAE model systems. Recently, a new class of T-cells, TH-17 cells, has been shown to regulate inflammation in EAE. This unique subset of T helper cells produce IL-17 and develops along a pathway that is distinct from that of TH-1 and TH-2 cell differentiation (Park et al., 2005). It has been demonstrated that neutralization of IL-17 with IL-17-receptor-Fc-protein or an IL-17 monoclonal antibody ameliorates the disease course of EAE (Hofstetter et al., 2005). The production of IL-17 requires upstream activation of IL-23, and neutralizing antibodies specific for... 

Interleukin 1 (IL-1) Endogenous pyrogen Monocytes/macs Th cells stimulates production of lymphokines, especially IL-2 and expression of IL-2R B cells proliferation and differentiation Macs stimulates production of cytokines, IL-1, IL-6, and tumor necrosis factor-a (TNF-a) Brain fever response... 

IL-2 T cell growth factor (GF) Th cells Th cells stimulates proliferation and release of lymphokines (especially Thi cells) B cells proliferation and differentiation NK cells activates... 

IL-5 T-cell-replacing factor (TRF) BCGF II Th cells B cells proliferation and differentiation stimulates IgA production... 

IL-6 IFN-ya Th cells Monocytes Endothelial cells Fibroblasts T cells proliferation and differentiation B cells proliferation and differentiation Others similar profile of activity to IL-1 synergizes with IL-1... 

The proliferation in step 3 can be repeated several times (i.e., clonal expansion ). Eventually, the lymphocytes will stop proliferating and will begin to differentiate into antigen-specific effector cells. As with proliferation, this step in an acquired immune response is under the control of lymphokines produced primarily by Th cells. One of the critical steps in the differentiation of B cells is the switch to the... 

The basis for the effector function by antigen-specific lymphocytes - especially antibody-secreting B cells, Td cells, and Tc cells - and the participation of other cellular components of the immune system in acquired immunity - including NK cells, macrophages, and neutrophils - have already been emphasized in other sections of this volume. It has also been emphasized that Th cells play an important effector role in acquired immunity as regulators in the growth and differentiation of B cells and Tc cells. In this regard, it is important to note that both populations of T cells whose participation in an acquired immune response is mediated by the secretion of lymph-okines, that is, Th and Tq cells, are characterized by the expression of CD4. 

The heterogeneity among Th cells is considerably more complex than a simple division into two discrete classes. Thl and Th2 cells must be regarded as being the most differentiated forms of CD4+ cells that develop from a common precursor or precursors as the immune response evolves. The immediate progenitor population is Th cells (designated ThO) that are... 

If cytokines are themselves instrumental in regulating the development of differentiated Th-cell populations, then an intriguing question arises as to the provenance of these cytokines before a mature immune response has evolved. In the case of Thl-cell development then presumably the stimulation by dendritic cell- and/or macrophage-derived IL-12 of IFN-y production by NK cells and the concerted action of IL-12 and IFN-yon Thl-cell precursors may provide one answer. One suggestion regarding the evolution of Th2-cell... 

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