Human thymus contains 2 distinct dendritic cell populations

Abstract

In this study, 2 distinct populations of mature dendritic cells (DCs) were identified in the human thymus. The major population is CD11b ؊ , CD11c ؉ , and CD45RO low and does not express myeloidrelated markers. It displays all the characteristics of mature DCs with a typical dendritic morphology, high surface levels of HLA-DR, CD40, CD83, and CD86, and expression of DC-lysosome-associated membrane glycoprotein messenger RNA (mRNA). In addition, CD11b ؊ thymic DCs do not express macrophage inflammatory protein-1␣ (MIP-1␣) mRNA, but express thymus-expressed chemokine (TECK) mRNA and are able to secrete bioactive interleukin 12 (IL-12) upon stimulation. In contrast, the minor and variable thymic DC population is CD11b ؉ , CD11c high , and CD45RO high and comprises CD83 ؉ CD14 ؊ mature and CD83 ؊ CD14 ؉ immature DCs. It expresses macrophage-colony stimulating factor receptor, MIP-1␣ mRNA and high amounts of decysin mRNA after CD40 activation, but does not express TECK and is a weak bioactive IL-12 producer. Also identified were the IL-3R␣ high plasmacytoid cells, which are present in the thymic cortex and medulla. Upon culture with IL-3, granulocyte/macrophage-colony stimulating factor, and CD40 ligand, the plasmacytoid cells can adopt a phenotype resembling that of freshly isolated CD11b ؊ thymic DCs. However, these plasmacytoid-derived DCs fail to secrete bioactive IL-12; therefore, conclusions cannot be made about a direct relation between thymic plasmacytoid cells and CD11b ؊ DCs. Whereas CD11b ؉ thymic DCs appear to be related to tonsillar germinal-center DCs, the major CD11b ؊ IL-12-secreting human thymus DC population has similarities to mouse CD11b ؊ CD8 ؉ DCs. IntroductionDendritic cells (DCs) are professional antigen presenting cells 1 that form a dynamic network throughout most tissues and organs and that are crucial for the immune surveillance of the body. [2][3][4] The current model is that Langerhans cells, immature DCs found in epithelia, are the precursors of mature "interdigitating" DCs, found in the T-cell zones of lymphoid organs. 5 Immature interstitial DCs in various tissues, such as the dermis, move into germinal centers as germinal center DCs (GCDCs). In the lymph nodes, tonsils, and spleen, the mature DCs present the antigen captured in the periphery to naive T cells and induce immunity. The DCs of the thymus have a somewhat different role, namely, to present selfantigens and induce negative selection of potential auto-reactive T-cell clones. 6 Until recently, the interdigitating DCs were considered a single population of mature DCs. However, this laboratory and others showed that distinct DC subsets of different lineage derivation and different functions 7-13 could be distinguished in mouse lymphoid organs. On the one hand, CD8 ϩ DCs, lacking myeloid markers such as CD11b and apparently arising from a lymphoid-committed progenitor, 14 are typically potent interleukin 12 (IL-12)-secreting mature DCs. 10,13,15 CD8 ϩ DCs are present at various levels in all mouse lymphoid organs and constitute...

Dendritic cells in the thymus contribute to T-regulatory cell induction

“…Three types of DCs are found in the mouse thymus (pDCs, Sirp␣ Ϫ CD8 ϩ TcDCs, and Sirp␣ ϩ CD8 Ϫ TcDCs), and these have counterparts in the human thymus (43). We show that the minor Sirp␣ ϩ TcDC subset is much more efficient than the other DCs at polyclonal T R induction in vitro.…”

Factors Contributing to HIV-1 Induced Pathogenesis in the Human Thymus

“…There are similarities but also differences between thymic and peripheral pDC. Both thymic and peripheral pDC respond, in addition to IL-3, also to GM-CSF (Ghirelli et al, 2010;Vandenabeele et al, 2001). Like the peripheral pDC, the thymic pDC have the capacity to develop into mature DC, but some differences were observed in the expression of certain cell surface antigens .…”

“…In the human thymus a cell type very similar to peripheral pDC was identified. These CD3 -cells express CD4, CD45RA and high levels of CD123 and are localized at the cortico-medullary junction and in the medulla (Bendriss-Vermare et al, 2001;Olweus et al, 1997;Schmitt et al, 2000;Vandenabeele et al, 2001). There are similarities but also differences between thymic and peripheral pDC.…”

“…Among the different types of DC subsets are pDC, which are present in cord and peripheral blood, T cell areas of the lymph nodes and in the medullary area of the thymus, and have the capacity to produce high levels of type I IFN, i.e. IFN and IFN in response to viruses and other stimuli (Bendriss-Vermare et al, 2001;Cella et al, 1999;Foster et al, 2000;Kadowaki et al, 2000;Olweus et al, 1997;Siegal et al, 1999;Vandenabeele et al, 2001). Type I IFNs are survival factors for pDC, while maturation of pDC depends on IL-3 (Grouard et al, 1997).…”

Auditing Protein Therapeutics Management by Professional APCs: Toward Prevention of Immune Responses against Therapeutic Proteins

“…However, the Langerhans cell (marked by Birbeck granules, CD1a, and langerin) is considered as a subtype in both murine and human systems. Evidences of similarity between mouse and human DCs also came from studies with the human thymus wherein most DCs are CD11c ϩ CD11b Ϫ CD45RO low , express many "myeloid markers," and thus resemble mouse thymic CD8 ϩ DCs (19,20). 3 Abbreviations used in this paper: DC, dendritic cell; PEGylation, derivatization of A protein with polyethylene glycol; Treg, regulatory T cell.…”