CD4+ T cells regulate CD8+ T cell-mediated cutaneous immune responses by restricting effector T cell development through a Fas ligand-dependent mechanism.
The magnitude and duration of CD8(+) T cell-mediated responses in the skin to hapten sensitization and challenge, contact hypersensitivity (CHS), is negatively regulated by CD4(+) T cells through an unknown mechanism. In this study we show that CD4(+) T cells restrict the development and expansion of hapten-specific CD8(+) T cells mediating CHS responses to 2,4-dinitrofluorobenzene. In the absence of CD4(+) T cells, high numbers of hapten-specific CD8(+) T cells producing IFN-gamma were detected in the skin-draining lymph nodes on day 5 postsensitization, and these numbers decreased slightly, but were maintained through day 9, correlating with the increased magnitude and duration of CHS responses observed in these mice. In the presence of CD4(+) T cells, the number of hapten-specific CD8(+) T cells producing IFN-gamma detected on day 5 postsensitization was lower and quickly fell to background levels by day 7. The limited development of effector CD8(+) T cells was associated with decreased numbers of hapten-presenting dendritic cells in the lymphoid priming site. This form of immunoregulation was absent after sensitization of Fas ligand-defective gld mice. Transfer of wild-type CD4(+) T cells to gld mice restored the negative regulation of CD8(+) T cell priming and the immune response to hapten challenge in gld-recipient mice. These results indicate that CD4(+) T cells restrict hapten-specific CD8(+) T cell priming for CHS responses through a Fas ligand-dependent mechanism.
Gorbachev
Anton V
AV
Department of Immunology and Urological Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA. gorbaca@ccf.org
Fairchild
Robert L
RL
D000279:Administration, Cutaneous; D000818:Animals; D017951:Antigen Presentation; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D003877:Dermatitis, Contact / Q000235:genetics / Q000276:immunology*; D004139:Dinitrofluorobenzene / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D053222:Fas Ligand Protein; D005260:Female; D006241:Haptens / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology*; D019014:fas Receptor / Q000378:metabolism*
D018984:Epitopes, T-Lymphocyte; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D006241:Haptens; D008024:Ligands; D008562:Membrane Glycoproteins; D019014:fas Receptor; D004139:Dinitrofluorobenzene