Thl cell-mediated immunity

Immunoangiostasis The Role of CXCR3/CXCR3 Ligand Biological Axis in Mediating Thl Cell-Mediated Immunity and Angiostasis... 

VI. THE CONCEPT OF TMMUNOANGIOSTASIS THE ROLE OF CXCR3/ CXCR3 LIGAND BIOLOGICAL AXIS IN MEDIATING THl CELL-MEDIATED IMMUNITY AND ANGIOSTASIS... 

The field of DNA vaccines centers on the ability to deliver genetic material, coding, for desired protein antigens in the context of a mammalian expression vector (Donnelly et al., 1997). It was realized that the immunostimulatory properties observed with DNA vaccines, namely the ability to induce a Thl biased or cell mediated immune response, was attributable in part to the presence of CpG motifs within the plasmid DNA (Klinman et al., 1997). In fact, it was demonstrated that the quality of immune activation by DNA vaccines could be influenced by the deliber-ate alteration of CpG content (Krieg et al., 1998). Further, with the identification of neutralizing CpG motifs it became possible to remove any neutralizing influence from the DNA vaccine plasmids. The end result was the optimization of DNA vaccine plasmids, with respect to immune activation (Krieg et al., 1998). 

The ability of dietary consumption of foods containing LAB to modulate immune responses has been thoroughly studied in animal models. Dietary consumption of LAB and Bifidobacteria strains have been shown to enhance protection against intracellular bacterial pathogens. Physiological responses have been shown to correspond with the cell-mediated immune responses that have the Thl cell bias. 

It is likely that IL-12 plays a pivotal role in the host defense against intraceUular pathogens. For example, it (1) promotes cell-mediated immunity by polarizing Th types of cytokine responses (causing DTHR), (2) enhances the lytic activity of NK and/or LAK cells, (3) augments specific Tc responses, (4) induces the production of IFNy, and (5) suppresses the development of Th2 types of cytokine responses and humoral immunity, particularly IgGl and IgE responses. Thus IL-12 selectively promotes differentiation of Thl lymphocytes and potentiates cell-mediated immunity while suppressing Th2-dependent functions, such as the production of IL-4, IL-10, and IgE antibodies. 

The observation that T-cell immune responses may be involved in the pathogenesis of occupational respiratory diseases is supported by animal models (Dearman et al., 1992). Rodents can be easily sensitized to LMW chemicals such as acid anhydrides and diisocyanates. A murine model has been used to study the differential production of cytokines by helper T-cell subsets (Thl and Th2) after exposure to different reactive chemicals. It has been shown that under normal conditions Thl lymphocytes primarily secrete IL-2, interferon-/and tumour necrosis factor J3 (TNI -/ ) whereas Th2 lymphocytes secrete IL-4, IL-5, IL-10 and IL-13. A predominance of Th2 cells correlated with IgE-mediated immune responses, while a predominance of Thl cells was associated with cell-mediated immune responses (Dearman et al., 1992). These investigators demonstrated preferential activation of Th2 cells by phthalic anhydride (PA), trunellitic anhydride (TMA) and diphenyl-methylene diisocyanate, indicating that chemical structure may be important for determining the quality of immune response elicited (Dearman et al., 1992). 

STAT proteins have been shown to be critically involved in inflammatory processes of several immune and proliferative disorders [26]. Among them, STAT-1 is activated in response to many lymphocyte-activating cytokines, mainly the interferons, and is essential for cell-mediated immunity. Interferon-y biases the immune system towards a so-called Thl response providing the rationale for the observation that exaggerating Thl responses predominantly underlie chronic inflammatory diseases. 

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