Inhibition of functional T cell priming and contact hypersensitivity responses by treatment with anti-secondary lymphoid chemokine antibody during hapten sensitization.
Recent studies have suggested a pivotal role for secondary lymphoid chemokine (SLC) in directing dendritic cell trafficking from peripheral to lymphoid tissues. As an extension of these studies, we examined the consequences of anti-SLC Ab treatment during Ag priming on T cell function in an inflammatory response. We used a model of T cell-mediated inflammation, contact hypersensitivity (CHS), where priming of the effector T cells is dependent upon epidermal dendritic cell, Langerhans cells, and migration from the hapten sensitization site in the skin to draining lymph nodes. A single injection of anti-SLC Ab given at the time of sensitization with FITC inhibited Langerhans cell migration into draining lymph nodes for at least 3 days. The CHS response to hapten challenge was inhibited by anti-SLC Ab treatment in a dose-dependent manner. Despite the inhibition of CHS, T cells producing IFN-gamma following in vitro stimulation with anti-CD3 mAb or with hapten-labeled cells were present in the skin-draining lymph nodes of mice treated with anti-SLC Ab during hapten sensitization. These T cells were unable, however, to passively transfer CHS to naive recipients. Animals treated with anti-SLC Ab during hapten sensitization were not tolerant to subsequent sensitization and challenge with the hapten. In addition, anti-SLC Ab did not inhibit CHS responses when given at the time of hapten challenge. These results indicate an important role for SLC during sensitization for CHS and suggest a strategy to circumvent functional T cell priming for inflammatory responses through administration of an Ab inhibiting dendritic cell trafficking.
Engeman
T M
TM
Department of Immunology, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Gorbachev
A V
AV
Gladue
R P
RP
Heeger
P S
PS
Fairchild
R L
RL
D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D002464:Cell Migration Inhibition; D054421:Chemokine CCL21; D019742:Chemokines, CC / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D003877:Dermatitis, Contact / Q000209:etiology / Q000276:immunology* / Q000517:prevention & control; D004139:Dinitrofluorobenzene / Q000008:administration & dosage / Q000276:immunology; D005260:Female; D006241:Haptens / Q000008:administration & dosage / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology; D007114:Immunization; D007275:Injections, Intravenous; D007801:Langerhans Cells / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010081:Oxazolone / Q000008:administration & dosage / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation
D000911:Antibodies, Monoclonal; C515479:Ccl21c protein, mouse; D054421:Chemokine CCL21; D019742:Chemokines, CC; D016207:Cytokines; D006241:Haptens; D010081:Oxazolone; D004139:Dinitrofluorobenzene