Abstract
The role of CD5 as a regulator of T cell signaling and tolerance is well recognized. Recent data show expression of CD5 on different subtypes of human dendritic cells, however its functional relevance in modulating DC mediated responses remains poorly understood. In this study, we show CD5 is expressed on CD11c+ DC from murine thymus, lymph node, spleen, skin and lung. Although the development of DC subpopulations in CD5-/- mice was normal, CD5-deficient DC produced significantly higher levels of IL-12 than wild type DC in response to LPS. CD5-/- DC, in comparison to CD5+/+ DC, enhanced the activation of CD4+ and CD8+ T cells in vitro and in vivo and induced significantly higher production of IL-2 and IFN-gamma by T cells. Consequently, CD5-/- DC were significantly more potent than wild type DC in the induction of anti-tumor immunity and contact hypersensitivity responses in mice. Restoration of CD5 expression in CD5-/- DC reduced IL-12 production and inhibited their capacity to stimulate T cells. Collectively, these data demonstrate that the specific expression of CD5 on DC inhibits the production of inflammatory cytokines and has a regulatory effect on their activity to stimulate T cells and induce immune responses. This study reveals a previously unrecognized regulatory role for CD5 on DC and provides novel insights into mechanisms for DC biology in immune responses.
Highlights
CD5 is a 67 kDa type 1 cell surface protein with a large cytoplasmic domain containing multiple potential phosphorylation sites that recruit regulators of T cell signaling [1, 2]
Migratory Dendritic cells (DC) in lymph node (LN) represent a population derived from the skin and they express a lower level of CD5 than resident DC
Our results show that CD5 deficiency significantly upregulates the production of IL-12 by Bone marrow derived dendritic cells (BMDC) and SP DC compared to WT DC (Fig 2B and 2C), a cytokine necessary for the differentiation of naïve CD4+ T cells into Th1 cells [43,44,45]
Summary
CD5 is a 67 kDa type 1 cell surface protein with a large cytoplasmic domain containing multiple potential phosphorylation sites that recruit regulators of T cell signaling [1, 2]. CD5 is expressed by thymocytes, mature T cells and the B1a subset of B cells [3]. CD5 regulates TCR signaling, tunes threshold for T cell activation during thymocyte development [4,5,6,7] and suppresses the activation of peripheral T cells through inhibition of TCR-proximal signaling in the immunological synapse [8, 9]. CD5 inhibits the function of dendritic cells. Universidad Nacional Autonoma de Mexico” and was supported by CONACYT (#513171). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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