T-cell helper function

Fraker PJ, DePasquale-Jardien P, et al. 1978. Regeneration of T cell helper function in zinc deficient adult mice. Proc Nat Acad Sci 75 5660-5664. 

SLE. An early hypothesis is that the prosthesis or injected silicone plays an adjuvant role by enhancing the immune response through increased macrophage and T-cell helper function. There is currently controversy as to whether silicone, as a foreign body, induces a nonspecific inflammation reaction, a specific cell-mediafed immunological reaction, or no reaction at all. However, there is strong support to indicate that silicone microparticles can act as haptens to produce a delayed hypersensitivity reaction in a genetically susceptible population of people. 

In view of the absence of T cell helper function in genetic non-responder animals, it appeared relevant to explore whether an antigen to which the response is under Ir gene control and which is unable to stimulate cellular immunity and T cell helper function in non-responder animals could nevertheless stimulate specific suppressor T cells. This possibility was first suggested by studies reported by Gershon et a/. . More recently, specific suppressor T cells have been demonstrated in our laboratory in GAT-primed non-responder j ice59,6o observed that injection of GAT to mice bearing the non-... 

Schaerli P, Willimann K, Lang AB, Lipp M, Loetscher P, Moser B. CXC chemokine receptor 5 expression defines follicular homing T cells with B cell helper function. J Exp Med 2000 192 1553-1562. 

Immunotoxicity. Metal fume fever is believed to be an immune response to zinc oxide. A correlation between the concentration of airborne zinc and the number of all types of T cells (helper, inducer, suppressor, and killer) in the bronchoalveolar lavage fluid of humans, possibly related to the onset of metal fume fever, was observed in an acute-duration inhalation study (Blanc et al. 1991). Impaired immune response in humans has been reported in an intermediate- duration oral study (Chandra 1984). No immune effects were observed in mice after oral exposure to zinc (Schiffer et al. 1991). There is some limited information to suggest that the immune system is a target of zinc toxicity. A battery of immune function tests after inhalation, oral, and dermal exposure to zinc compounds would be useful in determining if zinc is immunotoxic. 

Another more recently identified CD4 T cell snbset, termed follicular helper cells (Tfh), provides a helper function to B cells. Tfh cells are distinguished from Thl and Th2 cells by expression of the chemokine CXCR5, their asscxaalion with B cell follicles, and their B cell helper function. 

In fact, however, it must be pointed out that as yet the precise cellular locus of action of the antigen-specific T cell factor of Taussig and colleagues has not been defined and must be considered to be open at the moment. The fact that the latter factor works with bone marrow cells does not mean that its effect is directly on B cells since bone marrow is known to contain variable numbers of T cells and T cell precursors. Thus, the effect of the factor could be to facilitate maturation of precursor T cells to functional helper cells which would in turn cooperate with B cells. Moreover, it is possible that if the factor does indeed work directly on B cells, that this may be peculiar to immature B cells of bone marrow and not as much so in the case of more mature peripheral B lymphocytes. Further analysis is required to distinguish between these possibilities. 

Helper T cells (CD4+) are the great communicators of the immune response. Once activated, they proliferate and secrete cytokines that regulate effector cell function. Some helper T cells secrete cytokines that recruit cytotoxic T cells, B cells, or APCs, whereas others secrete cytokines that turn off the immune response once an antigen has been destroyed. 

Mosmann, T.R. and Coffman, R.L. (1989) Heterogeneity of cytokine secretion patterns and functions of helper T cells. Advances in Immunology 46, 111-147. 

Cells of the T cell lineage appear to be more sensitive to the immunomodulatory effects of Pb compared to other lymphoid populations. In addition, there are considerable differences in sensitivity across various T cell subpopulations [38 41], This differential sensitivity has become another major hallmark of Pb-induced immunotoxicity, although most data implicate T cells as indirect targets of Pb immunotoxicity. Both in vivo and in vitro observations of T-dependent immune responses in the presence of Pb suggest that T helper function and Th-dependent cytokines are skewed preferentially toward Th2 reactivities. Smith and Lawrence [42] found that Pb inhibited antigen presentation and stimulated a T cell clone of the Thl phenotype. McCabe and Lawrence [38] were the first to show that Pb inhibited Thl stimulation while it promoted presentation to Th2 clones. Heo and colleagues [39 41] provided both in vitro and in vivo results supporting this immunomodulation by Pb. 

Lymphocytes, the effector cells of the acquired immune system, include morphologically indistinguishable T and B cells, the former divided into CD4+ T helper cells and CD8+ cytotoxic T cells. Since the functions of those cell subsets differ so drastically, it became important to develop tools to distinguish them from each other. Efforts to identify cell subsets according to their expression of different surface antigens have been successful, including various Cluster of Determination (CD) markers (Table 23.1). In addition, cross-reactive monoclonal antibodies, and subsequently developed species-specific polyclonal and monoclonal antibodies towards the major histocompatibility complex (MHC) have been used to label cells in circulation and in tissue sections (Table 23.1). 

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