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Quantities of Interleukin‐12p40 in Mature CD8α 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 CD86highCD8α−DCs in spleen mainly produced IL‐12p40 after stimulation of high dose agonist. The ratio of CD40L positive T cells and IL‐12p40 secreting CD86highDCs 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 CD86highCD8α−DC via CD40.