Monocyte inflammatory protein-1 alpha facilitates priming of CD8(+) T cell responses to exogenous viral antigen.
Dendritic cells (DC) derived from bone marrow precursors of BALB/c or C57BL/6 mice in low-serum cultures supplemented with granulocyte macrophage colony stimulating factor and Flt(3) ligand were pulsed in vitro with hepatitis B surface antigen (HBsAg) particles. DC processed exogenous HBsAg and presented its MHC class I-binding epitopes to cytotoxic T lymphocytes (CTL). This specific and restricted interaction of DC with CTL stimulated release of IFN-gamma and macrophage inflammatory protein (MIP)-1 alpha from the responding CTL. MIP-1 alpha enhanced the survival of DC in vitro but did not induce proliferation. Furthermore, co-delivery of MIP-1 alpha facilitated CTL priming in vivo to exogenous HBsAg in low responder C57BL/6 (H-2(b)) mice: a single injection of a low dose of HBsAg particles (without further adjuvants) successfully primed K(b)-restricted CTL responses to HBsAg only when the exogenous antigen was co-delivered with 100 ng MIP-1 alpha. These in vitro and in vivo data point to an important role of MIP-1 alpha in the DC-dependent priming of CTL to exogenous viral antigens.
Flesch
I E
IE
Department of Medical Microbiology and Immunology, University of Ulm, Helmholtzstrasse 8/1, 89081 Ulm, Germany.
Stober
D
D
Schirmbeck
R
R
Reimann
J
J
D000276:Adjuvants, Immunologic; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002455:Cell Division; D002478:Cells, Cultured; D054407:Chemokine CCL4; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D015395:Histocompatibility Antigens Class I; D007371:Interferon-gamma / Q000032:analysis; D019402:Macrophage Inflammatory Proteins / Q000032:analysis / Q000276:immunology* / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014611:Vaccination
D000276:Adjuvants, Immunologic; D054407:Chemokine CCL4; D006514:Hepatitis B Surface Antigens; D015395:Histocompatibility Antigens Class I; D019402:Macrophage Inflammatory Proteins; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor