T lymphocytes potentiate murine dendritic cells to produce IL-12.
IL-12 is mainly produced by CD8alpha(+) dendritic cells (DCs) and induces Th1 polarization of the immune response. We investigated the influence of lymphocytes on splenic DC (SDC) and thymic DC (TDC) development and on their IL-12 production capacity. First, CD3epsilon(-/-) mice, lacking T cells, and RAG-2(-/-) mice, lacking T and B cells, possess numbers of SDCs, TDCs, and CD8alpha(+) SDCs similar to wild-type (WT) mice. Second, SDCs and TDCs from CD3epsilon(-/-) mice do not secrete IL-12 in vitro after different stimulations, whereas DCs from pTalpha(-/-) mice, possessing reduced T cell number, and RAG-2(-/-) mice, produce an IL-12 level similar to that of WT DCs. We show that T lymphocytes restore the capacity of DCs to produce IL-12 after stimulation in vivo by reconstitution of CD3epsilon(-/-) mice with WT T cells and in vitro by coculture of CD3epsilon(-/-) DCs with WT T cells. The regulation of IL-12 production occurred at the transcriptional level, with an increase of IL-12p35 transcripts and a decrease of IL-12p40 transcripts. Although IL-4 restores IL-12 production by CD3epsilon(-/-) SDCs, anti-IL-4 Abs inhibited only partially the IL-12 production in coculture of CD3epsilon(-/-) DCs and WT T cells. Taken together, these data show that T lymphocytes potentiate IL-12 production by DCs and that IL-4 is not solely involved in this regulation. In conclusion, B and T cells exert balanced actions on DCs by respectively inhibiting or promoting IL-12 production.
Rizzitelli
Alexandra
A
Laboratoire d'Immunochimie, Commissariat à l'Energie Atomique-Grenoble/Département Réponse et Dynamique Cellilaires, Institut National de la Santé et de la Recherche Médicale Unité 548, 17 rue des Martyrs, 38054 Grenoble cedex 9, France.
Berthier
Rolande
R
Collin
Véronique
V
Candéias
Serge M
SM
Marche
Patrice N
PN
D000818:Animals; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D016130:Immunophenotyping; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000235:genetics; D015847:Interleukin-4 / Q000502:physiology; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000096:biosynthesis; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000172:deficiency / Q000235:genetics; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D012333:RNA, Messenger; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D018664:Interleukin-12; D015847:Interleukin-4