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ß-Positive, Tc1 and Tc0 CD8+ T Cell Clones Mediate the In Vivo Inhibition of Rat IgE1
Department of Immunology, King’s College School of Medicine and Dentistry, London, United Kingdom
In the following study, we demonstrate that medium responder PVG
rats immunized i.p. with OVA complexed to the adjuvant aluminum
hydroxide exhibit a moderate IgE response (400–1000 ng/ml). In these
rats, we demonstrate that underlying the MHC class II-restricted
CD4+ T cell response, there is an MHC class
I-restricted CD8+ T cell component that plays an important
role in restricting the magnitude and duration of the IgE response. We
show that in vivo depletion of CD8+ T cells effects a
massive increase in IgE (20-fold), and that they are MHC class
I-restricted, OVA-specific, cytolytic cells that universally produce
IFN-
(25–69 ng/ml) and IL-2 (7.6–22 U/ml), and occasionally
secrete IL-4 (68–81 U/ml IL-4), and when adoptively transferred into
CD8-depleted recipients, can effect a significant reduction in IgE (3-
to 50-fold). We also demonstrate that this in vivo inhibition of IgE is
dependent on the Ag-specific activation of the CD8+ T
cells, and that the activated CD8+ T cells will suppress
total/bystander IgE in an Ag-nonspecific manner. These data are
consistent with a growing literature demonstrating sensitization of MHC
class I-restricted CD8+ T cells by exogenous protein Ags
delivered to mucosal sites, and may represent a mechanism whereby a
selective pressure can be applied on the functional outcome of an
immunoglobulin response to environmental allergens.
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