Distinct roles for B7-1 and B7-2 determinants during priming of effector CD8+ Tc1 and regulatory CD4+ Th2 cells for contact hypersensitivity.
Contact hypersensitivity (CHS) is a CD8+ T cell-mediated response to hapten sensitization and challenge of the epidermis. Both the IFN-gamma-producing effector CD8+ T cells and the IL-4/IL-10-producing CD4+ T (Th2) cells that restrict the magnitude and duration of the response are primed by hapten-presenting Langerhans cells (hpLC). hpLC isolated from hapten-sensitized animals expressed high levels of B7-2 and lower levels of B7-1, suggesting the availability of each molecule to provide costimulation during CD8+ and CD4+ T cell priming for CHS. Anti-B7-2 Ab given during hapten sensitization inhibited effector CD8+ and regulatory CD4+ T cell development and the magnitude of the CHS response. Cytokine production by CD8+ and CD4+ T cells was reduced in anti-B7-2 Ab-treated animals, indicating that costimulation for T cell development was not compensated by hpLC-expressed B7-1. Anti-B7-1 Ab inhibited CHS and increased the number of Th2 cells primed during hapten sensitization without inhibiting development of the IFN-gamma-producing CD8+ T cells. Depletion of CD4+ T cells, however, abrogated the inhibitory effect of anti-B7-1 Ab on the CHS response, indicating the amplified Th2 response mediated this inhibition. These results indicate a requirement for B7-2 costimulation by effector CD8+ and regulatory CD4+ T cells during priming for CHS. The ability of anti-B7-1 Abs to amplify the regulatory CD4+ Th2 component and inhibit CHS suggests a strategy to inhibit unwanted CD8+ T cell-mediated immune responses to Ags in the skin.
Xu
H
H
Department of Immunology, Cleveland Clinic Foundation, OH 44195-0001, USA.
Heeger
P S
PS
Fairchild
R L
RL
D000818:Animals; D018122:B7-1 Antigen / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D017449:Dermatitis, Allergic Contact / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D005434:Flow Cytometry; D007111:Immunity, Cellular; D051379:Mice; D008807:Mice, Inbred BALB C; D018418:Th2 Cells / Q000276:immunology*
D018122:B7-1 Antigen; D000939:Epitopes