title: CD4+ and CD8+ T cell priming for contact hypersensitivity occurs independently of CD40-CD154 interactions.
abstract: The primary effector cells of contact hypersensitivity (CHS) responses to dintrofluorobenzene (DNFB) are IFN-gamma-producing CD8(+) T cells, whereas CD4(+) T cells regulate the magnitude and duration of the response. The requirement for CD40-CD154 engagement during CD8(+) and CD4(+) T cell priming by hapten-presenting Langerhans cells (hpLC) is undefined and was tested in the current study. Similar CHS responses to DNFB were elicited in wild-type and CD154(-/-) animals. DNFB sensitization of CD154(-/-) mice primed IFN-gamma-producing CD8(+) T cells and IL-4-producing CD4(+) T cells. However, anti-CD154 mAb MR1 given during hapten sensitization inhibited hapten-specific CD8(+), but not CD4(+), T cell development and the CHS response to challenge. F(ab')(2) of MR1 failed to inhibit CD8(+) T cell development and the CHS response suggesting that the mechanism of inhibition is distinct from that of CD40-CD154 blockade. Furthermore, anti-CD154 mAb did not inhibit CD8(+) T cell development and CHS responses in mice depleted of CD4(+) T cells or in CD4(-/-) mice. During in vitro proliferation assays, hpLC from mice treated with anti-CD154 mAb during DNFB sensitization were less stimulatory for hapten-primed T cells than hpLC from either control mice or mice depleted of CD4(+) T cells before anti-CD154 mAb administration. These results demonstrate that development of IFN-gamma-producing CD8(+) T cells and the CHS response are not dependent on CD40-CD154 interactions. This study proposes a novel mechanism of anti-CD154 mAb-mediated inhibition of CD8(+) T cell development where anti-CD154 mAb acts indirectly through CD4(+) T cells to impair the ability of hpLC to prime CD8(+) T cells.
authors.affiliation: Department of Immunology, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
authors.forename: A V
authors.initials: AV
authors.lastname: Gorbachev
authors.forename: P S
authors.initials: PS
authors.lastname: Heeger
authors.forename: R L
authors.initials: RL
authors.lastname: Fairchild
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D017951:Antigen Presentation / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism*; D023201:CD40 Ligand / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D003877:Dermatitis, Contact / Q000276:immunology* / Q000517:prevention & control; D004139:Dinitrofluorobenzene / Q000008:administration & dosage / Q000276:immunology; D005260:Female; D006131:Growth Inhibitors / Q000008:administration & dosage; D006241:Haptens / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D007114:Immunization; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000096:biosynthesis; D007801:Langerhans Cells / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
chemical_list: D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D006131:Growth Inhibitors; D006241:Haptens; D023201:CD40 Ligand; D007371:Interferon-gamma; D004139:Dinitrofluorobenzene