Quantities of interleukin-12p40 in mature CD8alpha negative dendritic cells correlate with strength of TCR signal and determine Th cell development.
Strength of T cell antigen receptor (TCR) signaling drives the development of Th1 and Th2 subsets from naive T helper precursors. The quantity of interleukin-12 (IL-12) from antigen presenting cells (APC) is also profoundly involved in Th development. TCR signal strength and IL-12 production from dendritic cells (DCs) are linked by CD40 ligand (CD40L) expression on activated T cells. CD40L on the activated T cells interacts with CD40 on DC, resulting in induction of IL-12 from DCs. However, the subsets of DC in spleen that produce the IL-12 have not been clearly identified. Purification of DC subsets itself may provide maturation signals to immature DCs. Thus, we used non-purified mouse spleen cells to analyze IL-12 producing cells, near to steady states, during the interaction of naive T cells either with or without agonist. Mature CD86highCD8alpha- DCs in spleen mainly produced IL-12p40 after stimulation of high dose agonist. The ratio of CD40L positive T cells and IL-12p40 secreting CD86high DCs correlated with the concentration of agonist and Th1 development. However, anti-IL-12 did not completely inhibit the Th1 development. Altogether, strength of TCR signaling directs Th cell development by regulating CD40L expression on T cells which determines production of IL-12p40 from CD86high CD8alpha- DC via CD40.
Fujimoto
Noriki
N
Department of Pathology, Shiga University of Medical Science, Ohtsu, Shiga, Japan.
Ishida
Hideaki
H
Nakamura
Ichiro
I
Ogasawara
Kazumasa
K
Itoh
Yasushi
Y
D000818:Animals; D015703:Antigens, CD / Q000032:analysis / Q000276:immunology; D051940:B7-2 Antigen; D019013:CD40 Antigens / Q000378:metabolism; D023201:CD40 Ligand / Q000378:metabolism; D016827:CD8 Antigens / Q000032:analysis / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis / Q000378:metabolism*; D053762:Interleukin-12 Subunit p40; D015847:Interleukin-4 / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000032:analysis / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D021122:Protein Subunits / Q000096:biosynthesis / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D015703:Antigens, CD; D051940:B7-2 Antigen; D019013:CD40 Antigens; D016827:CD8 Antigens; C431698:CD8alpha antigen; C497965:Cd86 protein, mouse; D053762:Interleukin-12 Subunit p40; D008562:Membrane Glycoproteins; D021122:Protein Subunits; D011948:Receptors, Antigen, T-Cell; D023201:CD40 Ligand; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma