Human thymus contains 2 distinct dendritic cell populations

In vivo (Athens, Greece)

Dendritic cells play key roles in thymic histophysiology and histopathology. Therefore, we analyzed the immunotopographical distribution of cells expressing markers of dendritic cells and macrophages in postnatal human thymus. The streptavidin-biotin peroxidise-labeled (LSAB) and the double-LSAB/alkaline phosphatase/anti-alkaline phosphatase (APAAP) immunohistochemical procedures were used. S100 protein-, Cluster of designation 1a (CD1a)-, CD207-, CD11c- and CD123-positive cells, many of them exhibiting the morphology of dendritic cells, were detected in the cortex but mainly in the medulla. These markers, except CD123, were also detected in cells of juvenile and immature Hassall bodies. CD68- and CD163-positive cells were detected in the cortex and the medulla but not in Hassall bodies. The immunohistological detection of S100-, CD1a-, CD207- and CD11c-positive dendritic cells in juvenile and immature Hassall bodies may reflect an important role of these structures in the cooperati...

The Journal of Immunology, 2001

Dendritic cells (DC) are present at low density in the thymus where they mediate negative selection of self-reactive thymocytes. Previous reports suggest that thymic DC (TDC) are a single population of lymphoid-related DC. In this study, we documented the presence in the adult mouse thymus of an additional population of TDC exhibiting a myeloid phenotype (CD11c ؉ CD8␣ ؊ CD11b ؉). This population, which can be purified, represented ϳ20% of the total TDC and differs from the population of lymphoid TDC (CD11c ؉ CD8 ؉ CD11b ؊) by its incapacity to produce IL-12p70 under double stimulation by LPS and anti-CD40. Furthermore, using an original culture system allowing expansion of DC from myeloid progenitors, we demonstrated that DC exhibiting a similar myeloid phenotype can be derived from a common DC/macrophage progenitor resident in the adult mouse thymus. We found that, in contrast with myeloid splenic DC expanded in the same conditions, these cultured TDC were unable to produce IL-12p70 under double stimulation by LPS and anti-CD40 or LPS and IFN-␥. Thus, our results suggest that 1) adult mouse thymus contains at least two phenotypically and functionally distinct populations of DC; and 2) cultured myeloid DC derived from thymus and spleen differ by their ability to produce IL-12p70. The mechanisms underlying the differences in IL-12-secreting capacities of the cultured splenic and thymic DC are under current investigation.

Journal of Leukocyte Biology

We have previously shown that thymic CD34 ؉ cells have a very limited myeloid differentiation capacity and differentiate in vitro mostly into CD1a ؉-derived but not CD14 ؉-derived dendritic cells (DC). Herein we characterized the human neonatal thymic DC extracted from the organ in relationship with the DC generated from CD34 ؉ cells in situ. We show that in vivo thymic DC express E cadherin, CLA, CD4, CD38, CD40, CD44, and granulocyte-macrophage colony-stimulating factor-R (GM-CSF-R; CD116) but no CD1a. According to their morphology, functions, and surface staining they could be separated into two distinct subpopulations: mature HLA-DR hi , mostly interleukin-3-R (CD123)negative cells, associated with thymocytes, some apoptotic, and expressed myeloid and activation markers but no lymphoid markers. In contrast, immature HLA-DR ؉ CD123 hi CD36 ؉ cells with monocytoid morphology lacked activation and myeloid antigens but expressed lymphoid antigens. The latter express pT␣ mRNA, which is also found in CD34 ؉ thymocytes and in blood CD123 hi DC further linking this subset to lymphoid DC. However, the DC generated from CD34 ؉ thymic progenitors under standard conditions were pT␣-negative. Thymic lymphoid DC showed similar phenotype and cytokine production profile as blood/ tonsillar lymphoid DC but responded to GM-CSF, and at variance with them produced no or little type I interferon upon infection with viruses and did not induce a strict polarization of naive T cells into TH2 cells. Their function in the thymus remains therefore to be elucidated.

The Journal of Immunology, 2000

Immunobiology, 1984

Interdigitating cells: mononuclear phagocytes or dendritic cens? Interdigitating cells were first described as a morphologically separate entity of cells in 1970 by VELDMAN (1). The most prominent features distinguishing IDC from typical macrophages were a highly irregular surface with numerous blunt, interdigitating protrusions, a strikingly pale peripheral cytoplasm owing to perinuclear packing of the organelles and a localization almost exclusively to thymus-dependent areas of lymphoid tissue. Veldman's observations were later confirmed and extended to other species (2, 3, 4) including man (5). However, despite many dissimilarities between IDC and typical macrophages IDC were considered to belong to the mononuclear phagocyte system (2, 3, 4, 6, 7, 8) and to acquire their peculiar morphology as a consequence of T-cell influence (3, 7). These considerations implied that IDC develop from monocytes seeded out from the bone marrow, which is a requirement for membership in the mononuclear phagocyte system (9, 10). Although IDC have been shown to originate from the bone marrow (11), proof of IDC development from monocytes is still lacking. The last point is crucial as IDC have also been included in a group of bone-marrow derived non-lymphoid cells (NLC) that are postulated to be separate from the mononuclear phagocyte system (rev. in 12). Among these are the dendritic cells (DC) isolated from mouse spleen (13) and rat lymph nodes (14), the Langerhans cells (LhC) of the skin (15) and the veiled cells (VC) of peripheral lymph (16), here collectively referred to as dendritic NLC. These cells differ from typical macrophages in several respects, most notably by possessing a highly irregular, veiled or dendritic, surface and by showing low phagocytic ability (17, 18, 19). In addition, whereas most typical macrophages do not express surface la-antigens unless stimulated by T cells (20, 21), the dendritic NLC are constitutively strongly Ia+ (22,23, 24,25,26). In accordance with current views about the pivotal role played by la-antigens in stimulation of helper T cells (rev. in 27) typical macrophages can be stimulatory, inert or suppressive when tested for antigen Abbreviations: IDC = interdigitating cells; DC = dendritic cells; VC = veiled cells; NLC = non-lymphoid cells; APC = antigen-presenting cells; ACC = accessory cells.

Journal of Experimental Medicine, 2009

Many dendritic cells (DCs) in the normal mouse thymus are generated intrathymically from common T cell/DC progenitors. However, our previous work suggested that at least 50% of thymic DCs originate independently of these progenitors. We now formally demonstrate by parabiotic, adoptive transfer, and developmental studies that two of the three major subsets of thymic DCs originate extrathymically and continually migrate to the thymus, where they occupy a finite number of microenvironmental niches. The thymus-homing DCs consisted of immature plasmacytoid DCs (pDCs) and the signal regulatory protein α–positive (Sirpα+) CD11b+ CD8α− subset of conventional DCs (cDCs), both of which could take up and transport circulating antigen to the thymus. The cDCs of intrathymic origin were mostly Sirpα− CD11b− CD8αhi cells. Upon arrival in the thymus, the migrant pDCs enlarged and up-regulated CD11c, major histocompatibility complex II (MHC II), and CD8α, but maintained their plasmacytoid morphology...

Blood, 2010

The generation of natural regulatory T cells (nTregs) is crucial for the establishment of immunologic self-tolerance and the prevention of autoimmunity. Still, the origin of nTregs and the mechanisms governing their differentiation within the thymus are poorly understood, particularly in humans. It was recently shown that conventional dendritic cells (cDCs) in human thymus were capable of inducing nTreg differentiation. However, the function of plasmacytoid DCs (pDCs), the other major subset of thymic DCs, re-mains unknown. Here we report that pDCs resident in the human thymus, when activated with CD40 ligand (CD40L) plus interleukin-3, efficiently promoted the generation of CD4 ؉ CD25 ؉ Foxp3 ؉ nTregs from autologous thymocytes. The progenitors of these nTregs were selectively found within CD4 ؉ CD8 ؉ thymocytes that had accomplished positive selection, as judged by their CD69 hi TCR hi phenotype. Supporting the involvement of the CD40-CD40L pathway in pDC-induced nTreg generation, we show that positively se-lected CD4 ؉ CD8 ؉ progenitors specifically transcribed CD40L in vivo and upregulated CD40L expression on T-cell receptor engagement, thereby promoting the activation of pDCs. Finally, evidence is provided that nTregs primed by pDCs displayed reciprocal interleukin-10/transforming growth factor-␤ cytokine expression profiles compared with nTregs primed by cDCs. This functional diversity further supports a nonredundant tolerogenic role for thymic pDCs in the human thymus. (Blood. 2010;115(26):5366-5375)

Immunology and cell biology, 2015

Human thymus contains two major subpopulations of dendritic cells (DCs), conventional DCs (cDCs) and plasmacytoid DCs (pDCs), which are mainly involved in central tolerance and also in protecting the thymus against infections. In blood and peripheral organs cDCs include the subpopulation of BDCA3(hi) DCs, considered as equivalents to mouse CD8α(+) DCs. In this study we describe in human thymus the presence of a discrete population of BDCA3(hi) DCs that, like their peripheral counterparts, express CD13, low-intermediate levels of CD11c, CLEC9A, high levels of XCR1, IRF8 and TLR3, and mostly lack the expression of CD11b, CD14 and TLR7. Thymic BDCA3(hi) DCs display immature features with a low expression of costimulatory molecules and HLA-DR, and a low allostimulatory capacity. Also, BDCA3(hi) DCs exhibit a strong response to TLR3 stimulation, producing high levels of interferon (IFN)-λ1 and CXCL10, which indicates that, similarly to thymic pDCs, BDCA3(hi) DCs can have an important rol...

Immunology Letters, 1993

Mouse thymic dendritic cells (DC) have been isolated after collagenase digestion, selection of the low-density cell fraction, then depletion of Tlineage cells and other non-DC by treatment with specific monoclonal antibodies (mAb) and removal with anti-Ig-coated magnetic beads. The resulting DC preparation represented 0.1-0.2% of total thymic cells and contained 70-80% DC. Flow cytometry analysis of MHC class II (MHC II) expression by DC showed that 40% of DC expressed intermediate levels of MHC II, and 60% expressed high levels of this marker. Moreover, immunofluorescent 2-colour staining allowed the characterization of two clearly distinguishable DC subpopulations: MHC II inter DC were CD45 hi, CD44 hi, HSA hi, whereas MHC II hi DC were CD45 l°, CD44 I°, HSA l°. These results are discussed with regard to the functional significance of MHC II inter and MHC II hi DC subpopulations in the mouse thymus.