T helper cell cytokines

T Helper Cell Cytokine Responses During Intestinal Nematode Infection Induction, Regulation and Effector Function... 

Karpus, W.J., Lukas, N.W., Kennedy, K.J., Smith, W.S., Hurst, S.D. and Barrett, T.A. (1997) Differential C-C chemokine-induced enhancement of T helper cell cytokine production. Journal of Immunology 158, 4129-4136. 

Subramanian, G., Kazura, J.W., Pearlman, E., Jia, X., Malhorta, I. and King, C.L. (1997) B7-2 requirement for helminth induced granuloma formation and CD4 type 2 T helper cell cytokine expression. Journal of Immunology 158, 5914-5920. 

The direct effects opioid and opioidlike peptides exhibit on cells of the immune system is both varied and, in some instances, contradictory, depending on which receptor subtype is being studied. Mu and kappa receptors generally affect immunofunction in a suppressive manner, where delta receptors tend to express immunostimulation [82-85]. However, selected delta antagonists have shown to elicit suppressive effects on B-cell proliferation, NK cell activity, and T-helper cell cytokine production [86]. The alteration of leukocyte function via opioid receptors will be discussed highlighting specific cell subtype immunomodulation. Endorphin shows a inhibitory effect on splenocyte proliferation through central and peripheral autocrine/paracrine pathways [87]. 

Sato N, Ahuja SK, Quinones M, et al. CC chemokine receptor (CCR)2 is required for langerhans cell migration and localization of T helper cell type 1 (Thl)-inducing dendritic cells. Absence of CCR2 shifts the Leishmania major-resistant phenotype to a susceptible state dominated by Th2 cytokines, b cell outgrowth, and sustained neutrophilic inflammation. J Exp Med 2000 192(2) 205-218. 

The interleukin-2 receptor (IL-2R) is important in that the cytokine IL-2, secreted by a subset of T-helper cells, enhances the proliferation of activated T and B cells and increases the cytolytic activity of natural killer (NK) cells and the secretion of IgG. 

O Garra, A. (1998) Cytokines induce the development of functionally heterogeneous T helper cell subsets. Immunity 8, 275-283. 

It is also more or less accepted that T-cells, in particular T-helper cells (CD4+), may develop into either Thl cells or Th2 cells. By doing so, T-helper cells orchestrate the ensuing immune response by the types of cytokines they produce. Thl cells, by producing IL-12 and y-IFN, stimulate macrophages and/or cytotoxic T-cells to kill and destroy infected or malignant cells, or to initiate a delayed type hypersensitivity (DTH) reaction Th2 cells, by producing IL-4, IL-5, IL-10, IL-13, trigger B-cells to initiate antibody production. 

Stimulation for 24 hours with LPS leads to the release of interleukin-1 [3, IL-6, IL-8, TNF-a and by prolonging the incubation period from 48 to 72 hours, the whole blood model can detect the release of other lymphokines [45], including IL-2, IL-4, IL-13 and IFN-y. Skewing of the T-helper cell response to antigens can likewise be detected by evaluating the pattern of cytokine release, corresponding to a predominance of Th 1 or Th2 cytokine production. The predictive value of these approaches is currently under investigation. 

Figure 1.9. Interactions between macrophages and T helper cells. Stimulation of T helper cells results in the secretion of yinterferon, which then stimulates macrophages. The y interferon-stimulated macrophages then secrete Interleukin-1, which stimulates the T helper cells to secrete more yinterferon. Thus, a cytokine loop develops.

It is now recognised that the function of the immune system is carefully regulated by cytokines, small (8.5-40 kDa) proteins secreted by immune cells and by tissue cells such as endothelial cells and fibroblasts. T helper cells and macrophages are major sources of cytokines during inflammatory... 

Stumbles PA, Thomas JA, Pimm CL, Lee PT, Venaille TJ, Proksch S, Holt PG Resting respiratory tract dendritic cells preferentially stimulate T-helper cell type 2 (Th2) responses and require obligatory cytokine signals for induction of Thl immunity. J Exp Med 1998 188 2019-2031. 

Maggi E Abnormal production of T-helper 2 cytokines interleukin-4 and interleukin-5 by T cells from newborns with atopic parents. Eur J Immunol 1996 26 2293-2298. 33... 

Figure 17.18 Roles of APC, MHC-II and T-helper cell. The APCs phagocytose bacteria, digest them, and transfer the resultant pepb des plus MHC-II proteins to the surface of APC. The role of this is to present the pepb de, as an antigen, to the Th cells. The binding activates Th cells which then secrete cytokines. The activated Th cells now proliferate to produce many more identical Th cells to bind more of the antigens on the APCs. The roles of the cytokines are discussed below.

In this book, discussion is limited to their significance in coordination of the responses to an infection or in trauma. Although it is an oversimplihcation from the biochemical and clinical points of view, the cytokines can be separated into two classes those that are involved in the innate response (secreted by the macrophages, particularly during inflammation), and those involved in the responses of the adaptive system (secreted by the T-helper cells). Some of those secreted by T-lymphocytes and their effects are shown in Figure 17.20. Those secreted by macrophages and their effects are described in Figure 17.21. 

IL-2 (Proleukin) is a cytokine that promotes the proliferation, differentiation, and recruitment of T and B lymphocytes, natural killer cells, and thymocytes. Human recombinant IL-2 is designated as rIL-2. rIL-2 binds to IL-2 receptors on responsive cells and induces proliferation and differentiation of T helper cells and T cytotoxic cells. It also can induce B-lymphocyte proliferation, activate macrophage activity, and augment the cytotoxicity of natural killer cells. 

Also, it interferes with a chain of events, which initiates the immune response. This involves interaction of T-helper cells with the antigen-presenting cells (APCs), which causes activation, proliferation, and differentiation of T cells. A chain of events, which is necessary for this, includes receptor interactions and interaction with cytokines and intracellular transduction molecules. 

DPDPE has been found to have marked in vitro immunostimulant activity in patients suffering from leprosy and tuberculosis, enhancing antigen-stimulated proliferation of peripheral blood mononuclear cells and T-cell rosetting. DPDPE has been found to enhance cytokine production by T-helper cells, IL-6 production by macrophages and NK cell activity in murine splenocytes, suggesting immunostimulatory activity at low in vitro... 

Antigen-presenting cells (APCs) are a heterogeneous population of cells with extraordinary immunostimulatory capacity. Some play an important role in the induction of the function of T helper cells and some communicate with other lymphocytes. Cytokines can render the ability to present antigens to various cell types. This results in the expression of MHC class II molecules, which are sometimes lacking on some cells such as endothelial cells. The different types of APCs include macrophages, dendritic cells, B cells and interdigitating cells. APCs are mostly derived from bone marrow and are distributed in lymphoid tissues and in the skin. These three types of major APCs are also called professional APCs. 

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