Toxicology of Industrial Compounds

142 MECHANISMS OF PULMONARY SENSITIZATION
depress cell-mediated immunity (Powrie et al., 1993) and that Il–4 is able
to reduce significantly the severity of contact allergic reactions in mice
(Gautam et al., 1992).
Taken together the available data suggest that the selective stimulation
of Th cell responses and the consequent balance created between Th 1- and
Th 2-derived cytokines will have an important impact on both the induction
and elicitation stages of allergy. It is perhaps not surprising, therefore, that
there is increasing evidence for selective Th responses in human allergic
disease. Clones of T lymphocytes specific for aeroallergens such as house
dust mite and grass pollen, which cause IgE-mediated respiratory allergic
reactions in susceptible individuals, have been shown to elaborate Th 2
cytokines, but not IFN- (Parronchi et al., 1991). A predominance of the
Th 2-type cells has been found at sites of skin reactions in atopic individuals
(Kay et al., 1991) and increased numbers of IL-4 + T lymphocytes have been
identified in the nasal mucosa in allergen-induced rhinitis (Ying et al., 1994).
By contrast, human immune responses to nickel, a common cause of
allergic contact dermatitis, are characterized by the selective activation of
Th 1-type cells. Allergen-specific T lymphocyte clones isolated from the
peripheral blood of patients sensitized to nickel have been found to secrete
only low or undetectable amounts of IL-4 and IL-5, but high levels of IFN-
(Kapsenberg et al., 1991).
Although the relative contribution of Th 1 and Th 2 cells during immune
responses, and in particular the relative availability of IL-4 and IFN- , is
likely to play a predominant role in the regulation of IgE antibody, other
factors may be relevant. Not least, the priming of Th 1 cells for the
production of IFN- may in turn be dependent upon the action of another
cytokine, interleukin 12 (IL-12) (Manetti et al., 1994; Morris et al., 1994;
Schmitt et al., 1994). It has been demonstrated also that CD8 + T
lymphocytes exert an important immunoregulatory influence on IgE
responses (Kemeny et al., 1994; Renz et al., 1994), possibly via downregulation
of CD4 + Th 2 cell development (Noble et al., 1993).
It is clear that conditions outwith the immune system also influence the
magnitude of IgE responses. Certainly genetic predisposition is an
important, although poorly understood factor. In addition, there have been
suggestions that cigarette smoking and exposure to certain environmental
pollutants may result in increased IgE levels and may also serve to
aggravate asthma (Zetterstrom et al., 1981; Muranka et al., 1986;
Wardlaw, 1993).
Cell-mediated immune responses in chemical respiratory
allergy
The elicitation of chemical respiratory hypersensitivity may be associated
with both immediate-onset and late phase reactions. While IgE antibody