Flow cytometric analysis of cytokine receptors on human Langerhans' cells. Changes observed after short‐term culture

Larregina, Adriana T.; Morelli, Adrián E.; Kolkowski, E.; Fainboim, Leonardo

doi:10.1046/j.1365-2567.1996.451513.x

Cited by 45 publications

(23 citation statements)

References 41 publications

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“…It is well known that IL-1, TNF-a and C5a are all generated during the early phases of an inflammatory response and that epidermal rLC express IL-1R and 75 kD TNFR. 41 In this scene the upregulation of the C5aR on LC might be one of the components that might trigger LC migration and the subsequent adaptative immunity during an inflammatory process, as recently postulated by Katz and co-workers. 42 …”

Section: Discussionmentioning

confidence: 84%

Expression and modulation of C5a receptor (CD88) on skin dendritic cells. Chemotactic effect of C5a on skin migratory dendritic cells

et al. 1996

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SUMMARYAlthough it is known that dendritic cells (DC) migrate in response to inflammatory stimuli, there is little information about the expression of receptors for chemotactic factors on DC. The present study has demonstrated by double immunostaining and flow cytometry of Langerhan's cell (LC)-enriched epidermal cell suspensions that a small subpopulation (5-6%) of epidermal resident LC (rLC) expresses receptors for C5a (C5aR). Epidermal rLC positive for C5aR show a round-shape morphology, were located next to the basement membrane, and express HLA-DR molecules higher than C5aR negative rLC. These observations suggest that rLC would express C5aR as part of their process of maturation during tissue trafficking. To investigate whether epidermal LC up-regulate C5aR along their differentiation pathway, LC were differentiated in vitro after culture in epidermal cell suspensions supplemented with granulocyte-macrophage colony-stimulating factor (GM-CSF). As a result, in vitro differentiated LC increased the expression of C5aR up to 69% of the DC population. In accordance with this observation, interdigitating DC of secondary lymphoid organs (lymph node and tonsil) also expressed C5aR. Migratory CD1a positive DC that spontaneously migrated out of dermal or split-skin organ explants were also positive for C5aR and were used for chemotaxis and chemokinesis assays in response to human recombinant C5a (rC5a). Optimum migration to rC5a was observed at 10 ÿ 8 M with a sigmoidal dose-response curve. Checkboard analysis demonstrated that locomotion in response to rC5a was chemotaxis and not chemokinesis.

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Section: Discussionmentioning

confidence: 84%

Expression and modulation of C5a receptor (CD88) on skin dendritic cells. Chemotactic effect of C5a on skin migratory dendritic cells

et al. 1996

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“…It is generally accepted that induction of a cell-mediated immune response to papillomavirus occurs by cross-presentation of papillomavirus antigen by Langerhans cells (LCs), professional antigen-presenting cells (APCs) within the epidermis (44). LCs and dermal dendritic cells, the other professional APCs in the skin, are both derived from the myeloid lineage and express a functional ␥c subunit (31,32). A recent report has suggested that Toll-like receptor signaling through APCs may be an important component in the immune response to papillomavirus infection (56).…”

Section: Discussionmentioning

confidence: 99%

Severe Papillomavirus Infection Progressing to Metastatic Squamous Cell Carcinoma in Bone Marrow-Transplanted X-Linked SCID Dogs

Goldschmidt¹,

Kennedy

et al. 2006

J Virol

115

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Canine X-linked severe combined immunodeficiency (XSCID) is due to mutations in the common gamma chain (␥c) gene and is identical clinically and immunologically to human XSCID, making it a true homologue of the human disease. Bone marrow-transplanted (BMT) XSCID dogs not only engraft donor T cells and reconstitute normal T-cell function but, in contrast to the majority of transplanted human XSCID patients, also engraft donor B cells and reconstitute normal humoral immune function. Shortly after our initial report of successful BMT of XSCID dogs, it soon became evident that transplanted XSCID dogs developed late-onset severe chronic cutaneous infections containing a newly described canine papillomavirus. This is analogous to the late-onset cutaneous papillomavirus infection recently described for human XSCID patients following BMT. Of 24 transplanted XSCID dogs followed for at least 1 year post-BMT, 71% developed chronic canine papillomavirus infection. Six of the transplanted dogs that developed cutaneous papillomas were maintained for >3 1/2 years post-BMT for use as breeders. Four of these six dogs (67%) developed invasive squamous cell carcinoma (SCC), with three of the dogs (75%) eventually developing metastatic SCC, an extremely rare consequence of SCC in the dog. This finding raises the question of whether SCC will develop in transplanted human XSCID patients later in life. Canine XSCID therefore provides an ideal animal model with which to study the role of the ␥c-dependent signaling pathway in the response to papillomavirus infections and the progression of these viral infections to metastatic SCC.Severe combined immunodeficiency (SCID) is a heterogeneous group of diseases characterized by the inability to mount humoral and cell-mediated immune responses, and it is invariably fatal within the first 2 years of life (9, 46). X-linked SCID (XSCID) is the most common form of the disease, representing approximately 50% of all human SCID cases (9, 18). XSCID is caused by mutations in the common gamma (␥c) subunit of the receptors for interleukin-2 (IL-2), IL-4, IL-7, IL-9, IL-15, and IL-21 (reviewed in references 4 and 34). Thus, the XSCID phenotype is the complex result of multiple cytokine defects. The shared usage of the ␥c subunit by receptors for growth factors that are critical for normal B-, NK-, and T-cell development and function explains the profound immunologic abnormalities and clinical severity of the disease.Since the first successful HLA-identical bone marrow transplant in a boy with SCID in 1968 (19), bone marrow transplantation (BMT) has become the treatment of choice for all forms of SCID (10,18,22). SCID patients receiving a histocompatible (HLA-identical) BMT have Ͼ90% long-term survival rates (10,18,22). However, the majority of patients do not have a histocompatible donor. Haploidentical (half-matched) BMT with T-cell depletion to prevent fatal graft-versus-host disease has become the standard therapy for SCID patients who lack a histocompatible donor (10,18,22). Although T-cell depletion...

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“…39 Single cell suspensions were cultured for 24 h in complete medium. For CTL cytokine secretion assays, only heat-inactivated human AB serum was used throughout the procedure.…”

Section: Preparation Of Epidermal Cell Suspensionsmentioning

confidence: 99%

Direct transfection and activation of human cutaneous dendritic cells

et al. 2001

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Gene therapy techniques can be important tools for the induction and control of immune responses. Antigen delivery is a critical challenge in vaccine design, and DNA-based immunization offers an attractive method to deliver encoded transgenic protein antigens. In the present study, we used a gene gun to transfect human skin organ cultures with a particular goal of expressing transgenic antigens in resident cutaneous dendritic cells. Our studies demonstrate that when delivered to human skin, gold particles are observed primarily in the epidermis, even when high helium delivery pressures are used. We demonstrate that Langerhans cells resident in the basal epidermis can be transfected, and that

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Flow cytometric analysis of cytokine receptors on human Langerhans' cells. Changes observed after short‐term culture

Cited by 45 publications

References 41 publications

Expression and modulation of C5a receptor (CD88) on skin dendritic cells. Chemotactic effect of C5a on skin migratory dendritic cells

Expression and modulation of C5a receptor (CD88) on skin dendritic cells. Chemotactic effect of C5a on skin migratory dendritic cells

Severe Papillomavirus Infection Progressing to Metastatic Squamous Cell Carcinoma in Bone Marrow-Transplanted X-Linked SCID Dogs

Direct transfection and activation of human cutaneous dendritic cells

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