International Immunology, Vol 10, 1273-1279, Copyright © 1998 by Oxford University Press
R Romieu, M Baratin, M Kayibanda, JG Guillet and M Viguier
CD8+ T lymphocytes are involved in protective immune responses to infected
or tumor cells. In this report, we examined the regulation of
antigen-specific CD8+ T cell frequency and avidity by distinct Th cell
subsets. Peptide-specific CD8+ T cells were induced by immunization of mice
with a MHC class I-restricted epitope, co-injected with a MHC class
II-restricted epitope to recruit Th cells. CD8+ T cell responses were
assessed directly ex vivo for lytic activity and IFN-gamma secretion using
the enzyme-linked immunospot (ELISPOT) assay. Co- immunization in
incomplete Freund's adjuvant (IFA) with three different helper peptides
induced IFN-gamma- and IL-2-secreting Th cells, in the absence of IL-4
secretion, suggesting preferential Th1 profiles. Such immunization resulted
in the increase of antigen-specific CD8+ T cell frequency, which was
detected in blood as efficiently as in lymph nodes and spleen, and elicited
high-avidity CD8+ T cells. We investigated whether these effects were
dependent upon a particular Th profile. When alum was used instead of IFA,
the production of IL-2 by Th cells was still significant, while the
production of IFN-gamma was undetectable. Such Th cell activation failed to
support an increase of antigen- specific CD8+ T cell frequency. Altogether,
these results document in vivo the regulatory role played by Th cells in
CD8+ T cell activation and may be relevant for the design of efficient
vaccination schedules.
ARTICLES
IFN-gamma-secreting Th cells regulate both the frequency and avidity of epitope-specific CD8+ T lymphocytes induced by peptide immunization: an ex vivo analysis
INSERM U445, Institut Cochin de Genetique Moleculaire, Universite Rene Descartes, Paris, France.
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