Immunology and HIV expression in skin, in vitro, and in response to ultraviolet light

HIV can enter the body through Langerhans cells, dendritic cells, and macrophages in skin mucosa, and spreads by lysis or by syncytia. Since UVL induces of HIV-LTR in transgenic mice mid in cell lines in vitro, we hypothesized that UVB may affect HIV in people and may affect HIV in T cells in relation to dose, apoptosis, and cytokine expression. To determine whether HIV is induced by UVL in humans, a clinical study of HIV+ patients with psoriasis or pruritus was conducted during six weeks of UVB phototherapy, Controls were HIV-psoriasis patients receiving UVB and HIV+ KS subjects without UVB.Blood and skin biopsy specimens were collected at baseline, weeks 2 and 6, and 4 weeks after UVL. AIDS-related skin diseases showed unique cytokine profiles in skin and serum at baseline. In patients and controls on phototherapy, we observed the following: (1) CD4+ and CD8+ T cell numbers are not significantly altered during phototherapy, (2) p24 antigen levels, and also HIV plasma levels increase in patients not on antiviral therapy, (3) HIV-RNA levels in serum or plasma. (viral load) can either increase or decrease depending on the patient's initial viral load, presence of antivirals, and skin type, (4) HIV-RNA levels in the periphery are inversely correlated to serum IL-10 and (5) HIV+ cell in skin increase after UVL at 2 weeks by RT-PCR in situ hybridization mid we negatively correlated with peripheral load. To understand the mechanisms of UVB mediated HIV transcription, we treated Jurkat T cell lines stably transfected with an HIV-LTR-luciferase plasmid only or additionally with tat-SV-40 early promoter with UVB (2 J/m2 to 200 J/m2), 50 to 200 ng/ml rhIL-10, and 10 μg/ml PHA as control. HIV promoter activity was measured by luciferase normalized to protein. Time points up to 72 hours were analyzed for HIV-LTR activation. HIV-LTR activation had the following properties: (1) requires the presence of Tat, (2) occurs at 24 hours, and (3) is UVB dose dependent. Changes in viability by MTS (3-(4,5-dimethyhhiazol-2-y1)-5-(3-carboxymethoxyphonyl)-2-(4-sulfophenyl)-2H-tetrazolium) mixed with PMS (phenazine methosulfate) solution and apoptosis by propidium iodide and annexin V using flow cytometry (FC) were seen in irradiated Jurkat cells. We determined that (1) rhIL-10 moderately decreased HIV-LTR activation if given before radiation and greatly decreases it when given after UVB, (2) HIV-LTR activation was low at doses of greater than 70 J/m2, compared to activation at 50 J/m2. (Abstract shortened by UMI.)^

„Die Italiener aber sind weiss“: Philipp Christoph Kaysers musikalische Pilgerfahrt von Zürich nach Italien

Philipp Christoph Kayser ist vor allem als Freund Goethes bekannt. Er war bis ca. 1785 sein Hauskomponist. Seine Reiseberichte an Goethe sind für die Wahrnehmung der italiensichen Musik durch einen deutschen Komponisten von zentraler Bedeutung.

Geballte Faust, Doppelaxt, rosa Winkel. Gruppenkonstituierende Symbole der Frauen-, Lesben- und Schwulenbewegung

2008 jährte sich die Zäsur von 1968 zum 40. Mal. Besonders an diesem Jahrestag war, dass nun die nächste Generation in die gesellschaftliche Reflexion eingetreten ist. Das aus Vertretern der nach 1968 Geborenen bestehende Schweizer Ausstellungsbüro Palma3 hat aus diesem Anlass gemeinsam mit dem Historischen Museum in Frankfurt am Main die Ausstellung „Die 68er. Kurzer Sommer – lange Wirkung“ realisiert. Im Rahmen von acht Themenbereichen, die die wichtigsten Aufbrüche von 1968 und ihre Weiterentwicklung in den 1970er Jahren dokumentieren und reflektieren, nahm der Bereich „Geschlechterrollen“ einen besonderen Raum ein. Er präsentierte materialreich die Frauen-, Lesben- und Schwulenbewegung sowie die so genannte sexuelle Revolution der 1960er und 1970er Jahre in der Bundesrepublik Deutschland in ihren spannungsvollen Wechselverhältnissen. Im Zentrum des Beitrages sollen die unterschiedlichen Symbole dieser Bewegungen stehen. Diese dokumentieren anschaulich das Aushandeln gruppenkonstituierender Identitäten, wobei Rückgriffe auf ältere Symbole und deren Transformationen sowie Neukontextualisierungen zu beobachten sind. In der Frauenbewegung war das Venus-/Weiblichkeitszeichen mit geballter Faust im Innern in verschiedenen Versionen als grafische Verbindung von linker Bewegung und Feminismus verbreitet. Zwei ineinander verschlungene Weiblichkeitssymbole stehen in der Lesbenbewegung für weib-weibliche Sexualität. Dass die Frauen- und die Lesbenbewegung teilweise eine enge Allianz eingegangen sind, lässt sich auch an ihren gemeinsamen Symbolen ablesen: Die Labrys (Doppelaxt), eine minoische Kultaxt, repräsentiert die Autonomie und Stärke der Amazonen, als deren Waffe sie gilt. Das alte Zeichen der beiden gegeneinander gestellten Hände stellt eine Vagina dar und wurde ursprünglich von Männern als obszöne Geste für den Geschlechtsverkehr benutzt, wobei die Hände in Höhe ihrer Geschlechtsorgane gehalten wurden. In der Frauen- und Lesbenbewegung wurde dieses Zeichen mit erhobenen Armen über dem Kopf gezeigt, um die sexuelle Selbstbestimmung der Frauen deutlich zu machen. Demgegenüber greift die Schwulenbewegung auf den rosa Winkel als Symbol zurück. Dieser kennzeichnete während des Nationalsozialismus’ männliche Häftlinge in Konzentrationslagern als homosexuell. Er wurde von der deutschen Schwulenbewegung aufgegriffen und in emanzipatorischer Absicht umgewertet, wobei die nationalsozialistische Vergangenheit des Symbols präsent bleiben sollte. Insbesondere in den frühen 1970er Jahren finden sich unterschiedlichste Entwürfe dieser Symbole auf Flugblättern, Broschüren, Zeitschriften, Büchern, Plakaten und Transparenten. An Hand einzelner Gruppierungen wie der Homosexuellen Aktion Westberlin, die als Schwulen- und Lesbenorganisation gegründet worden war, sich jedoch schnell in die HAW und das LAZ (LesbenAktionsZentrum) aufsplittete, der Frauenorganisation Brot und Rosen und der Roten Zelle Schwul (ROTZSCHWUL) soll der Aushandlungsprozess innerhalb der Gruppierungen sowie das Verhandeln von Gruppenidentität und -inszenierung nach innen und außen nachgezeichnet werden. Zugleich lässt sich das Weiterexistieren bzw. Verschwinden der jeweiligen Symbole wie auch das Entstehen neuer Symbole – beispielsweise der Regenbogenfahne – als Indiz für die Veränderungen innerhalb der Bewegungen und deren Selbstwahrnehmung und Selbstinszenierung lesen.

Polycystic Kidneys and GM2 Gangliosidosis-Like Disease in Neonatal Springboks (Antidorcas marsupialis)

Clinical, gross, histopathologic, electron microscopic findings and enzymatic analysis of 4 captive, juvenile springboks (Antidorcas marsupialis) showing both polycystic kidneys and a storage disease are described. Springbok offspring (4 of 34; 12%) were affected by either one or both disorders in a German zoo within a period of 5 years (2008-2013). Macroscopic findings included bilaterally severely enlarged kidneys displaying numerous cysts in 4 animals and superior brachygnathism in 2 animals. Histopathologically, kidneys of 4 animals displayed cystic dilation of the renal tubules. In addition, abundant cytoplasmic vacuoles with a diameter ranging from 2 to 10 μm in neurons of the central and peripheral nervous system, hepatocytes, thyroid follicular epithelial cells, pancreatic islets of Langerhans and renal tubular cells were found in 2 springbok neonates indicative of an additional storage disease. Ultrastructurally, round electron-lucent vacuoles, up to 4 μm in diameter, were present in neurons. Enzymatic analysis of liver and kidney tissue of 1 affected springbok revealed a reduced activity of total hexosaminidase (Hex) with relatively increased HexA activity at the same level of total Hex, suggesting a hexosaminidase defect. Pedigree analysis suggested a monogenic autosomal recessive inheritance for both diseases. In summary, related springboks showed 2 different changes resembling both polycystic kidney and a GM2 gangliosidosis similar to the human Sandhoff disease. Whether the simultaneous occurrence of these 2 entities represents an incidental finding or has a genetic link needs to be investigated in future studies.

DNA damage-induced Fas ligand expression by epidermal dendritic cells mediates UV-induced immune suppression of contact hypersensitivity

Exposure to UVB radiation induces local and systemic immune suppression, evidenced by inhibition of the contact hypersensitivity response (CHS). Epidermal dendritic cells, the primary antigen presenting cells responsible for the induction of CHS, are profoundly altered in phenotype and function by UVB exposure and possess UV-specific DNA damage upon migrating to skin-draining lymph nodes. Expression of the proapoptotic protein FasL has been demonstrated in both skin and lymph node cells following UVB exposure. Additionally, functional FasL expression has recently been demonstrated to be required in the phenomenon of UV-induced immune suppression. To test the hypothesis that FasL expression by DNA-damaged Langerhans cells migrating to the skin-draining lymph nodes is a crucial event in the generation of this phenomenon, mice were given a single 5KJ/m2 UV-B exposure and sensitized to 0.5% FITC through the exposed area. Dendritic cells (DC) harvested from skin-draining lymph nodes (DLN) 18 hours following sensitization by magnetic CD11c-conjugated microbeads expressed high levels of Iab, CD80 and CD86, DEC-205 and bore the FITC hapten, suggesting epidermal origin. Radioimmunoassay of UV-specific DNA damage showed that DC contained the vast majority of cyclobutane pyrimidine dimers (CPDs) found in the DLN after UVB and exhibited increased FasL mRNA expression, a result which correlated with greatly increased FasL-mediated cytotoxicity. The ability of DCs to transfer sensitization to naïve hosts was lost following UVB exposure, a phenomenon which required DC FasL expression, and was completely reversed by cutaneous DNA repair. Collectively, these results demonstrate the central importance of DNA damage-induced FasL expression on migrating dendritic cells in mediating UV-induced suppression of contact hypersensitivity. ^

Na 1 Nachlass Max Horkheimer, 32 - Korrespondenzen mit Familie Lehmann (p. I 16, 236-480)

6 Briefe zwischen E. Lederer und Max Horkheimer, 1936-1939; 1 Brief von Theodor W. Adorno an Minna Ledermann, 26.04.1941; 1 Brief von W. W. Lee an Max Horkheimer, 15.11.1938; 69 Brief zwischen Berta Lehmann, Flora Lehmann an Max Horkheimer, 1939-1944; 2 Briefe von Berta Lehmann, Flora Lehmann an Juliette Favez, März 1939; 1 Brief vom Reisebüro Anselm Stuttgart an Max Horkheimer, 02.04.1941; 4 Briefe zwischen der Auswandererstelle Marx Stuttgart und Max Horkheimer, 28.11.1940, 1941; 1 Brief von Max Horkheimer an Karl Adler, 24.01.1941; 2 Briefe von Max Horkheimer an Walter C. Louchheim, 1940; 5 Briefe zwischen dem American Consul General Stuttgart und Max Horkheimer, 1939-23.11.1940; 4 Brief zwischen der Auswandererstelle Adler Stuttgart und Max Horkheimer, 1940; 2 Briefe zwischen der Auswandererstelle Stuttgart und Max Horkheimer, 20.02.1940; 5 Briefe zwischen N. C. Leites und Max Horkheimer, 17.05.1937, 1937; 4 Briefe zwischen Irmgard Lenel und Max Horkheimer, 1941, 1942; 3 Briefe zwischen Heidi Lenssen und Max Horkheimer, 01.02.1937, 1937; 3 Briefe zwischen Theo F. Lentz und Max Horkheimer, 05.07.1945, 1945; 11 Briefe zwischen Jella Lepman und Max Horkheimer,1939-1941; 2 Briefe von Max Horkheimer an das American Consul General London, 1941; 1 Brief von R. Leppla an Max Horkheimer, 21.06.1948; 7 Briefe zwischen Max Lerner und Max Horkheimer, 1941, 1942; 5 Briefe und Beilagen zwischen Adolf Laschnitzer und Max Horkheimer, 1939-1940; 2 Briefe ziwschen dem The Emergency Committee in Aid of Displaced Foreign Scholars, New York und Max Horkheimer, 23.110.1940, 07.11.1940; 3 Briefe und 1 Beilage zwischen Andrée Lespiaut und Max Horkheimer, 13.11.1948; 1 Brief von Max Horkheimer an A. Lesser, 21.05.1935; 1 Brief von Bobby Level und Frank Level an Max Horkheimer, 20.07.1949; 1 Brief von Julius Walter Levi an Max Horkheimer, 15.05.1940; 1 Brief von Bernhard W. Levmore an Leo Löwenthal, 13.08.1940; 3 Briefe von Margot von Mendelssohn an Bernhard W. Levmore, 1940; 3 Briefe zwischen Ernst Levy und Max Horkheimer, 21.05.1927, 1937; 1 Brief von Erwin Levy an Max Horkheimer, 23.03.1935; 17 Briefe zwsichen Hanna Levy und Max Horkheimer, Friedrich Pollock, 1936-1937; 6 Briefe zwischen Herbert Levy und Friedichpollock, 1939-1940; 1 Brief von Friedrich Pollock an Heinz Langerhans, 11.08.1939; 2 Briefe von Max Horkheimer an die Society of the Protection of Science and Learning, The Scott Polar Research Institut, Cambridge, England, 24.11.1939; 2 Briefe zwischen Marie Levy und Max Horkheimer, 18.12.1938, 03.08.1939; 10 Briefe und 1 Beilage zwischen Max Lexandrowitz, Magarete Lexandrowitz und Max Horkheimer, 1940; 1 Brief vom National Refugee Service New York an Max Horkheimer, 19.03.1940; 1 Rechnung vom Librairie Generale de Droit & de Jurisprudence Paris an Max Horkheimer, 18.05.1938; 2 Briefe zwsichen L. Lichtwitz und Max Horkheimer, 16.04.1936, 25.07.1938;

Na 1 Nachlass Max Horkheimer, 665 - "Research Project on Anti-Semitism" (p. IX 101-IX 112)

Institute of Social Research; "Research Project on Anti-Semitism. General Statement of Scope of Project, Fields to be investigated, First Assignements, Plan of Operation, Joint Conferences" (15.3.1943), a) Typoskript, 5 Blatt, b) Typoskript, 3 Blatt, c) Typoskript mit handschriftlichen Ergänzungen, 5 Blatt; Institute of Social Research: "Notes on Some Methodological Principles and Some Tentative Assumptions for the Work of the Anti-Semitism Project" (15.3.1943), Typoskript, 3 Blatt; "Project on Anti-Semitism. Excerpt from a letter of D.R. (American Jewish Committee), dated 3/31/43" (31.03.1943), Typoskript mit handschriftlichen Ergänzungen, 2 Blatt; Institute of Social Research: "Research Project on Anti-Semitism. General Statement of Scope of Project, Fields to be investigated, First Assignements etc. Supplement: Los Angeles Group" (26.4.1943), a) Typoskript mit handschriftlichen Ergänzungen, 13 Blatt, b) Typoskript, 13 Blatt, c) Typoskript, 8 Blatt; Heinz Langerhans: "Methods to Evaluate the Attitude of Different Sections of the German Population toward Institutionalized Antisemitism" (6.5.1943), Typoskript mit eigenhändiger Korrektur, 5 Blatt; "Discussion with Messrs. George Mintzer and Newman Levy on present day U.S.A. Antisemitism" (5.3.1943), a) Typoskript, 4 Blatt b) Typoskript mit handschriftlichen Korrekturen, 4 Blatt; Re.: Antisemitism Project. Statement of Expense 15.03.1943 - 15.06.1943, Preliminary Budget 15.06.1943 - 15.03.1944, Aufstellungen für das American Jewish Committee, 15.06.1943, 4 Blatt; Paul Massing: "Some Notes to Fineberg's 'Overcoming Antisemitism'" (16.06.1943), Typoskript, 4 Blatt; "Luncheon with Mr. Hexter. Present: Dr. Pollock, Weil, Gurland, Massing and Mr. Hexter. Purpose: Discussion of S.A. Fineberg's book 'Overcoming Antisemitism'" (17.06.1943), Typoskript, 2 Blatt; "Luncheon with Mr. R.C. Rothschild in the Yale Club", Über Antisemitismus in den USA, 28.6.1943, Typoskript mit handschriftlichen Korrekturen, 1 Blatt; Friedrich Pollock: Memoranden über Besprechungen mit R.C. Rothschild, betreffs Anti-Semitism-Project (September 1943): 1. "Remarks of Mr. Rothschild concerning our Psychological Study in a meeting between him, P. and L." (21.9.1943); 2. "Memorandum on work's progress of Anti-Semitism-Project" (15.09.1943), Typoskript, 1 Blatt; 3. "Meeting R.C. Rothschild and Pollock", (15.09.1943), Typoskript, 2 Blatt; 4. "Memorandum No. 1" (14.09.1943), Typoskript, 1 Blatt; "Memorandum re: Antisemitism Project" (29.10.1943), Typoskript mit handschriftlichen Ergänzungen, 2 Blatt;

Na 1 Nachlass Max Horkheimer, 672 - Forschungsprojekte über Antisemitismus, Vorurteil, Autorität: Einzeluntersuchungen (p. IX 136a-IX 138)

Gumperz, Julian: Resumé zu "Autorität und Familie", Entwurf, 1937?; a) Typoskript, 6 Blatt; b) Typoskript mit handschriftlichen Korrekturen, 6 Blatt; "Untersuchung über die Autoritätseinstellung von Studentinnen eines New Yorker Colleges", März 1937. Typoskript, 2 Blatt; Langerhans, Heint (?): "Verhalten der deutschen Bevölkerung gegenüber dem Antisemitischen-Programm der Nazi-Regierung"; Nicht vor 1942. Typoskript mit handschriftlichen Korrekturen, 104 Blatt [unzutreffender Autorenvermerk von Friedrich Pollock: H. Marcuse?]; Dupont, Grete: "Conversations with Antisemits", Gesprächsprotokolle und zusammenfassender Bericht, Mai-Oktober 1943, Typoskript, 87 Blatt; siehe auch IX 143;

Investigation of the mechanism of increased melanoma incidence in UV -irradiated mouse skin

The availability of transplantable, syngeneic murine melanomas made it possible to study the potential effects of UV radiation on the growth and progression of melanomas in an animal model. The purpose of my study was to determine how UV-irradiation increases the incidence of melanoma out-growth, when syngeneic melanoma cells are transplanted into a UV-irradiated site. Short term intermittent UVB exposure produces a transitory change in the mice which allows the increased outgrowth of melanoma cells injected into the UV-irradiated site. One possible mechanism is an immunomodulatory effect of UVR on the host. An alternative mechanism to account for the increased tumor incidence in the UV-irradiated site, is the release of inflammatory mediators from UV-irradiated epidermal cells. A third possibility is that UVR could induce the production and/or release of melanoma-specific growth factors resulting in increased melanoma outgrowth.^ My first step in distinguishing among these different possible mechanisms was to characterize further the conditions leading to increased development of melanoma cells in UV-irradiated mouse skin. Next, I attempted to determine which of the 3 proposed mechanisms was most likely. To do this, I defined the specificity of the effect by examining the growth of additional C3H tumorigenic cell lines in UV-irradiated skin. Second, I determined the immunogenicity of these tumor cell lines. The tumor cell lines exhibiting increased tumor incidence are restricted to those tumor cell lines which are immunogenic in normal C3H mice. Third, I determined the effect of UVR on melanoma development did not occur in immunosuppressed mice.^ Because of results from these three lines of investigation suggested that the effect was immunologically mediated, I then investigated whether specific immune reactions were affected by local UV irradiation. To accomplish this, I investigated the effect of UVR on cutaneous immune cells and on induction of contact hypersensitivity (CHS), and I also determined the effect of UVR on the development and the expression of systemic immunity against the melanoma cells. There is no clear cut relationship between the number of Langerhans or Thy1+ cells and the UV effect on tumor incidence. Furthermore, there was no suppression of CHS in the UV-irradiated mice. While the development of systemic immunity is significantly reduced, it appears to be sufficient to provide in vivo immunity to tumor challenge. However the elicitation of tumor immunity in immunized mice can be abrogated if tumor challenge occurs in the site of UV irradiation. This investigation provides new information on an effect of UVR on the elicitation of tumor immunity. Furthermore, it indicates that UV radiation can play a role in the development of melanoma other than just in the transformation of melanocytes. ^

Investigation of mechanisms involved in ultraviolet B radiation-induced, T cell -mediated immune suppression

Cutaneous exposure to ultraviolet-B radiation (UVR) results in the suppression of cell-mediated immune responses such as contact hypersensitivity (CHS) and delayed-type hypersensitivity (DTH). This modulation of immune responses is mediated by local or systemic mechanisms, both of which are associated with the generation of antigen-specific suppressor T lymphocytes (Ts). UV-induced Ts have been shown to be CD3+CD4+CD8 − T cells that control multiple immunological pathways. However, the precise mechanisms involved in the generation and function of these immunoregulatory cells remain unclear. We investigated the cellular basis for the generation of UV-induced Ts lymphocytes in both local and systemic models of immune suppression, and further examined the pleiotrophic function of these immunoregulatory cells. ^ We used Thy1.1 and Thy1.2 congenic mice in a draining lymph node (DLN) cell transfer model to analyze the role played by epidermal Langerhans cells in the generation of Ts cells. We demonstrate that T cells tightly adhered to antigen-presenting cells (APC) from UV-irradiated skin are the direct progenitors of UV-induced Ts lymphocytes. Our studies also reveal that UV-induced DNA-damage in the form of cyclobutyl pyrimidine dimers (CPD) in the epidermal APC is crucial for the altered maturation of these adherent T cells into Ts. ^ We used TCR transgenic mice in an adoptive transfer model and physically tracked the antigen-specific clones during immune responses in unirradiated versus UV-irradiated mice. We demonstrate that UV-induced Ts and effector TDTH cells share the same epitope specificity, indicating that both cell populations arise from the same clonal progenitors. UVR also causes profound changes in the localization and proliferation of antigen-specific T cells during an immune response. Antigen-specific T cells are not detectable in the DLNs of UV-irradiated mice after 3 days post-immunization, but are found in abundance in the spleen. In contrast, these clones continue to be found in the DLNs and spleens of normal animals several days post-immunization. Our studies also reveal that a Th2 cytokine environment is essential for the generation of Ts in UV-irradiated mice. ^ The third part of our study examined the pleiotrophic nature of UV-induced Ts. We used a model for the induction of both cellular and humoral responses to human gamma-globulin (HGG) to demonstrate that UV-induced Ts lymphocytes can suppress DTH as well as antibody responses. (Abstract shortened by UMI.) ^

Distribución de las células presentadoras de antígenos en las glándulas salivales

Las células presentadoras de antígenos profesionales como las células de Langerhans o las células dendríticas intersticiales del tejido conectivo, son las células capturadoras de antígenos más importantes del sistema inmune. En trabajos previos describimos variaciones numéricas y estructurales de las células dendríticas; con especial referencia a las células de Langerhans, en diversos epitelios del tracto digestivo. El propósito de este trabajo fue estudiar la distribución, en forma comparativa, de las células dendríticas en glándulas salivales mayores y menores de la mucosa oral. Material y métodos: para esta investigación se utilizaron muestras de glándulas salivales mayores y menores tomadas de ratas Wistar. Las muestras fueron procesadas utilizando técnicas de microscopía óptica convencional, electrónica e inmunohistoquímica. Los resultados muestran numerosas células dendríticas en los conductos salivares excretores (con epitelio estratificado) así como en el parénquima glandular. Aunque no detectamos diferencias estadísticas significativas entre los dos componentes glandulares analizados, nuestros hallazgos sugieren que, debido a su localización, estas células cumplen un rol fundamental en las defensas inmunes de la mucosa oral.

Dendritic cell ontogeny: A human dendritic cell lineage of myeloid origin

Dendritic cells (DC) have been thought to represent a family of closely related cells with similar functions and developmental pathways. The best-characterized precursors are the epidermal Langerhans cells, which migrate to lymphoid organs and become activated DC in response to inflammatory stimuli. Here, we demonstrate that a large subset of DC in the T cell-dependent areas of human lymphoid organs are nonactivated cells and belong to a separate lineage that can be identified by high levels of the interleukin 3 receptor α chain (IL-3Rαhi). The CD34+IL-3Rαhi DC progenitors are of myeloid origin and are distinct from those that give rise to Langerhans cells in vitro. The IL-3Rαhi DC furthermore appear to migrate to lymphoid organs independently of inflammatory stimuli or foreign antigens. Thus, DC are heterogeneous with regard to function and ontogeny.