Lipopolysaccharide enhances in vivo interleukin-2 production and proliferation by naive antigen-specific CD4 T cells via a Toll-like receptor 4-dependent mechanism.
Microbial adjuvants are essential for the development of T-cell-dependent antibody production, recall T-cell proliferation and interferon-gamma production following immunization with protein antigens. Using an adoptive transfer approach, we showed that the adjuvant lipopolysaccharide enhanced the frequency of cells producing interleukin-2, enhanced clonal expansion by antigen-specific CD4 T cells and increased CD86 and interleukin-1alpha production by antigen-presenting cells. All of these effects were dependent on Toll-like receptor-4 (TLR4) expression by cells other than the antigen-specific CD4 T cells. The ability of lipopolysaccharides to increase the number of antigen-specific CD4 T cells that survive after immunization probably explains the previous finding that antigen-specific proliferation by T cells from normal mice depends on previous exposure to antigen and adjuvant.
Costalonga
Massimo
M
Department of Developmental and Surgical Sciences, School of Dentistry, University of Minnesota, Minneapolis, MN 55455, USA. costa002@umn.edu
Zell
Traci
T
D000276:Adjuvants, Immunologic; D019264:Adoptive Transfer; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D004306:Dose-Response Relationship, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D007376:Interleukin-2 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051197:Toll-Like Receptor 4 / Q000276:immunology*
D000276:Adjuvants, Immunologic; D018984:Epitopes, T-Lymphocyte; D007376:Interleukin-2; D008070:Lipopolysaccharides; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4