title: Deficient contact hypersensitivity reaction in CD4-/- mice is because of impaired hapten-specific CD8+ T cell functions.
abstract: Mice deficient in the CD4 molecule (CD4-/-) are widely used to evaluate the requirement for CD4+ T cell help in viral, tumoral, and transplantation immunity. Previous studies, showing that CD4-/- mice develop impaired contact hypersensitivity (CHS) responses, have suggested that CD4+ T cells are required for the optimal induction of this skin inflammatory reaction. other studies have, however, demonstrated that CHS was mediated by CD8+ T cells, without the need for CD4+ T cell help. Here, we show that CD4-/- mice develop a normal delayed-type hypersensitivity response to protein antigen, which is mediated by major histocompatibility molecules class II-restricted CD4-CD8- T cells, but a decreased CHS response to 2,4-dinitro-fluorobenezene. Analysis of the hapten-specific T cell pool demonstrates that priming of CD8+ T cells occurred normally in CD4-/- mice, as assessed by specific proliferative responses and interferon-gamma (IFN-gamma) production of purified CD8+ T cells. Furthermore, CD8+ T cells were able to adoptively transfer a normal CHS reaction. In contrast, total lymph node cells from CD4-/- mice showed decreased IFN-gamma production and diminished specific cytotoxic T lymphocytes (CTL) activity, which could be reversed by in vitro restimulation with hapten-pulsed class II-deficient antigen-presenting cells. These data confirm that class I-restricted CD8+ T cells can fully develop in effectors of CHS in the absence of CD4+ T cell help and suggest that the impaired CHS in CD4-/- mice is because of the presence of a class II-restricted T cell subset, which controls CHS by inhibiting hapten-specific CTL responses.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) U503, Lyon Cedex, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Saint-Mezard
authors.forename: Cyril
authors.initials: C
authors.lastname: Chavagnac
authors.forename: Marc
authors.initials: M
authors.lastname: Vocanson
authors.forename: Jeanne
authors.initials: J
authors.lastname: Kehren
authors.forename: Aurore
authors.initials: A
authors.lastname: Rozières
authors.forename: Sophie
authors.initials: S
authors.lastname: Bosset
authors.forename: Marius
authors.initials: M
authors.lastname: Ionescu
authors.forename: Bertrand
authors.initials: B
authors.lastname: Dubois
authors.forename: Dominique
authors.initials: D
authors.lastname: Kaiserlian
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Nicolas
authors.forename: Frédéric
authors.initials: F
authors.lastname: Bérard
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D015704:CD4 Antigens / Q000235:genetics*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D003877:Dermatitis, Contact / Q000235:genetics* / Q000276:immunology*; D006241:Haptens / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology
chemical_list: D015704:CD4 Antigens; D006241:Haptens; D000949:Histocompatibility Antigens Class II; D007371:Interferon-gamma