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.
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.
Romieu
R
R
INSERM U445, Institut Cochin de Génétique Moléculaire, Université René Descartes, Paris, France.
Baratin
M
M
Kayibanda
M
M
Guillet
J G
JG
Viguier
M
M
D000595:Amino Acid Sequence; D000818:Animals; D000915:Antibody Affinity / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D007114:Immunization; D007371:Interferon-gamma / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology*; D016176:T-Lymphocyte Subsets; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism*
D018984:Epitopes, T-Lymphocyte; D010455:Peptides; D007371:Interferon-gamma