Instruction of naive CD4+ T cells by polarized CD4+ T cells within dendritic cell clusters.
Cooperation between CD4(+) T cells can enhance the response and modulate the cytokine profile, and defining these parameters has become a major issue for multivalent-vaccine strategies. We explored cooperation using adoptive transfer of two populations of TCR transgenic T cells of different specificity. One was transferred without prior activation, whereas the second was activated for five days by antigen stimulation under polarizing culture conditions. Both populations were transferred into a single adoptive host and then primed by particle-mediated DNA delivery. Polarized Th1 cells (inducers) raised the frequency of IFN-gamma(+) cells within a naive (target) population, whereas Th2 inducers raised the frequency of IL-4(+) and reduced that of IL-2(+) cells. These effects were obtained when the genes for both antigens were on the same particle, favoring presentation by the same dendritic cell, but not when on different particles delivered to different dendritic cells. Autonomy of DC clusters allows linked sets of antigens (e.g. from a single pathogen) to maintain cytokine bias, but allows other independent responses, each with their own set of autonomous clusters.
Creusot
Rémi J
RJ
Department of Immunology and Molecular Pathology, Windeyer Institute of Medical Sciences, University College London, GB.
Biswas
Jason S
JS
Thomsen
Lindy L
LL
Tite
John P
JP
Mitchison
N Avrion
NA
Chain
Benjamin M
BM
D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D019470:Biolistics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002645:Chickens; D010856:Columbidae; D003433:Crosses, Genetic; D003574:Cytochrome c Group / Q000235:genetics / Q000276:immunology; D004274:DNA, Recombinant / Q000008:administration & dosage; D003713:Dendritic Cells / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D007114:Immunization; D007156:Immunologic Memory / Q000276:immunology; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D019041:L-Selectin / Q000032:analysis; D037181:Lectins, C-Type; D008198:Lymph Nodes / Q000166:cytology* / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D018448:Models, Immunological; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000637:transplantation; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D003574:Cytochrome c Group; D004274:DNA, Recombinant; D018984:Epitopes, T-Lymphocyte; D007371:Interferon-gamma; D007376:Interleukin-2; D015847:Interleukin-4; D019041:L-Selectin; D037181:Lectins, C-Type; D010047:Ovalbumin; D011948:Receptors, Antigen, T-Cell; D000099192:CD69 Antigens