*3.3. Downstream T Cell Commitment by mDCs*

After successful antigen presentation by DCs, the interaction between mDCs and T cells in lymph nodes occurs to initiate cell-mediated adaptive immune responses. Further T cell commitments, such as proliferation and differentiation, are regulated by the level of TCRs triggered by antigen-presenting mDCs and the effectiveness of the signal amplification the T cells receive [57]. Several types of important mDC-mediated signals in lymph nodes are required for the activation and differentiation of naïve T cells. (1) The peptide– MHC complex initiates antigen-dependent signal transduction, (2) costimulatory molecules (i.e., B7 molecules, CD40, or ICAM-1) amplify the signaling process, and even a low level of available antigens effectively induces TCR-dependent T cell commitment [73,74], and (3) soluble cytokines facilitate further T cell activity

One of the crucial cytokine signals, IL-2 produced by activated Th1 cells, upregulates T cell proliferation. The direct activation of CD8<sup>+</sup> T cells, and the subsequent expansion of T cell populations upon TCR activation, is mediated by autocrine and paracrine IL-2 signaling [75,76]. IL-2 also promotes the differentiation of effector T cells [77]. Moreover, the duration of sustained TCR stimulation is controlled by the secretion of IL-12 by mDCs, which promote the progression of T cell differentiation and the subsequent formation of terminally differentiated effector cells. Specifically, in the presence of IL-12, T cells can develop into Th1 cells or Th2 cells, and these T helper cell populations gain the ability to move to inflamed organs to perform their own roles as effectors [78]. The stability of the mDC–T cell synapse maintains the duration of the stimulation during the signaling and transduction processes [79]. For instance, CD4<sup>+</sup> T cells need to be in contact with mDCs for 24 h to induce efficient cell division [80]. Even when naïve CD8<sup>+</sup> T lymphocytes interacted with mDCs for only 8 h, they exhibited a stronger proclivity for differentiating into effector and memory T cells [81,82].
