Human skin dendritic cells in health and disease.

Dendritic cells (DCs) are specialized antigen presenting cells abundant in peripheral tissues such as skin where they function as immune sentinels. Skin DCs migrate to draining lymph node where they interact with naïve T cells to induce immune responses to microorganisms, vaccines, tumours and self-antigens. In this review, we present the key historical developments and recent advances in human skin DC research. We also integrate the current understanding on the origin and functional specializations of DC subsets in healthy skin with findings in inflammatory skin diseases focusing on psoriasis and atopic eczema. A comprehensive understanding of the dynamic changes in DC subsets in health and disease will form a strong foundation to facilitate the clinical translation of DC-based therapeutic and vaccination strategies.

Langerin-expressing dendritic cells in human tissues are related to CD1c+ dendritic cells and distinct from Langerhans cells and CD141high XCR1+ dendritic cells.

Langerin is a C-type lectin expressed at high level by LCs of the epidermis. Langerin is also expressed by CD8(+)/CD103(+) XCR1(+) cross-presenting DCs of mice but is not found on the homologous human CD141(high) XCR1(+) myeloid DC. Here, we show that langerin is expressed at a low level on DCs isolated from dermis, lung, liver, and lymphoid tissue and that langerin(+) DCs are closely related to CD1c(+) myeloid DCs. They are distinguishable from LCs by the level of expression of CD1a, EpCAM, CD11b, CD11c, CD13, and CD33 and are found in tissues and tissue-draining LNs devoid of LCs. They are unrelated to CD141(high) XCR1(+) myeloid DCs, lacking the characteristic expression profile of cross-presenting DCs, conserved between mammalian species. Stem cell transplantation and DC deficiency models confirm that dermal langerin(+) DCs have an independent homeostasis to LCs. Langerin is not expressed by freshly isolated CD1c(+) blood DCs but is rapidly induced on CD1c(+) DCs by serum or TGF-ß via an ALK-3-dependent pathway. These results show that langerin is expressed outside of the LC compartment of humans and highlight a species difference: langerin is expressed by the XCR1(+) "DC1" population of mice but is restricted to the CD1c(+) "DC2" population of humans (homologous to CD11b(+) DCs in the mouse).

Human dendritic cell subsets.

Dendritic cells are highly adapted to their role of presenting antigen and directing immune responses. Developmental studies indicate that DCs originate independently from monocytes and tissue macrophages. Emerging evidence also suggests that distinct subsets of DCs have intrinsic differences that lead to functional specialisation in the generation of immunity. Comparative studies are now allowing many of these properties to be more fully understood in the context of human immunology.

Langerhans cells down-regulate inflammation-driven alveolar bone loss.

Excessive bone resorption is frequently associated with chronic infections and inflammatory diseases. Whereas T cells were demonstrated to facilitate osteoclastogenesis in such diseases, the role of dendritic cells, the most potent activators of naive T cells, remains unclear. Using a model involving inflammation-driven alveolar bone loss attributable to infection, we showed that in vivo ablation of Langerhans cells (LCs) resulted in enhanced bone loss. An increased infiltration of B and T lymphocytes into the tissue surrounding the bone was observed in LC-ablated mice, including receptor activator of NF-κB ligand (RANKL)-expressing CD4(+) T cells with known capabilities of altering bone homeostasis. In addition, the absence of LCs significantly reduced the numbers of CD4(+)Foxp3(+) T-regulatory cells in the tissue. Further investigation revealed that LCs were not directly involved in presenting antigens to T cells. Nevertheless, despite their low numbers in the tissue, the absence of LCs resulted in an elevated activation of CD4(+) but not CD8(+) T cells. This activation involved elevated production of IFN-γ but not IL-17 or IL-10 cytokines. Our data, thus, reveal a protective immunoregulatory role for LCs in inflammation-induced alveolar bone resorption, by inhibiting IFN-γ secretion and excessive activation of RANKL(+)CD4(+) T cells with a capability of promoting osteoclastogenesis.

Estudo comparativo de mastócitos e células de Langerhans na doença periodontal em indivíduos HIV-positivos e negativos / Comparative study of Langerhans cells and mast cells in disease periodontal individuals to HIV-positive and negative

Este estudo tranversal, teve como objetivo avaliar quantitativamente e comparar a densidade e a frequência dos mastócitos c-kit+ e triptase+ e das células de Langerhans S100+ por meio da técnica de imunoistoquímica na gengivite e periodontite em indivíduos HIV-positivos e negativos. Adicionalmente, buscou-se avaliar a correlação entre a densidade e frequência destas células com níveis sanguíneos de linfócitos T (LT) CD4, CD8 e carga viral, nos indivíduos HIV-positivos. A amostra constou de 50 biópsias, divididos em quatro grupos: 1) 15 indivíduos com periodontite crônica moderada (PCM) HIV-positivos, 2) 15 indivíduos com PCM HIV-negativos, 3) 10 indivíduos com gengivite (G) HIV-positivos e 4) 10 indivíduos HIV-negativos com G. Todos os indivíduos HIV-positivos eram usuários de HAART (Highly Active Antiretroviral Therapies). Uma diminuição na frequência de mastócitos triptase+ com o aumento da inflamação tanto na gengivite com na periodontite foi observada em ambos os grupos. Não houve diferença na densidade e na frequência de mastócitos c-kit+ e triptase+ entre os grupos e neste caso, verificou-se uma diminuição com o aumento da inflamação apenas entre os casos de gengivite nos HIV-negativos. Na análise das células de Langerhans totais S100+, observou-se maior contagem no grupo com periodontite HIV-positivos em relação ao grupo com periodontite HIV-negativos. Ao realizar a análise por localização tecidual, não se observou diferença na contagem de células S100+. Não foi observado um aumento na contagem das células S100+ com o aumento da inflamação. Não houve correlação entre as células S100+, mastócitos c-kit e triptase+, com níveis sanguíneos de LT CD4, CD8 e carga viral. O uso de HAART parece ser a responsável pela manutenção de uma resposta imune eficaz nos indivíduos HIV-positivos. Desta forma, propicia densidade e frequência de mastócitos semelhantes com indivíduos HIV-negativos no tecido gengival acometido por gengivite e periodontite...

Histiocytic subpopulations in the gastrointestinal tract: distribution and possible relationship to function.

The distribution of specific histiocyte subsets within the human gastrointestinal tract has not been extensively characterized. Our goal was to immunohistochemically evaluate the distribution and location of CD1a-positive, CD68-positive, and Factor XIIIa (FXIIIa)-positive histiocyte subsets within the normal gastrointestinal tract and attempt to relate distribution to possible function. Twenty-nine samples of normal esophagus, stomach, small bowel, large bowel, and anus were routinely processed and immunohistochemically stained with antibodies to CD68, CD1a, and FXIIIa. The distribution and histologic location of histiocyte subsets were qualitatively analyzed. CD1a-positive cells were seen exclusively within anal and esophageal squamous mucosa. CD68 positive histiocytes were present in lamina propria and submucosa throughout the gastrointestinal tract and in Peyer patches. FXIIIa-positive histiocytes were also abundant in lamina propria and submucosa throughout the gastrointestinal tract, particularly around pericryptal sheaths and in parafollicular regions surrounding Peyer patches. Our results showed that there are distinct subpopulations of gastrointestinal histiocytes, and that distribution varies according to both cell type and site. Because Langerhans cells are epidermal antigen processing/presentation cells, their exclusive presence in squamous mucosa suggests an analogous function there. The prominence of both CD68 and FXIIIa-positive cells surrounding glandular pericryptal sheaths suggests that they are important to immune function at this mucosal interface and may play a role in communication between glands and lamina propria. In addition, the presence of specific histiocyte subsets within Peyer patches and para-follicular regions suggests that they are involved in different aspects of antigen processing associated with gut lymphoid tissue. Further studies are needed to explore the relation between specific histiocyte subsets and gastrointestinal disease processes.

Antigen-presenting cells in human periodontal disease tissues.

T cells are present in the inflammatory infiltrates of periodontal disease lesions and require antigen presentation by antigen-presenting cells (APCs). While it is still not known whether Th1 or Th2 cells predominate in these lesions, it has been reported that different APCs may induce activation of different T-cell subsets. An immunoperoxidase technique was used to investigate the presence of CD1a+, CMRF-44+, CMRF-58+ and CD83+ dendritic cells, CD14+ macrophages or dendritic cell precursors and CD19+ B cells in gingival biopsies from 21 healthy or gingivitis and 25 periodontitis subjects. The samples were divided into three groups according to the size of infiltrate (group 1, small infiltrates; group 2, medium infiltrates; group 3, extensive infiltrates). The presence of numerous CD1a+ Langerhans cells was noted in the epithelium with no differences between the healthy/gingivitis and periodontitis groups. The percentage of CD83+ dendritic cells in the infiltrates was higher than the percentage of CD1a+, CMRF-44+ or CMRF-58+ dendritic cells. Endothelial cells positive for CD83 were found predominantly in areas adjacent to infiltrating cells, CD83+ dendritic cells being noted in the region of CD83+ endothelium. The percentage of CD14+ cells in the inflammatory infiltrates was similar to that of CD83+ dendritic cells. B cells were the predominant APC in group 2 and 3 tissues. The percentage of B cells in group 3 periodontitis lesions was increased in comparison with group 1 periodontitis tissues and also in comparison with group 3 healthy/gingivitis sections. Functional studies are required to determine the roles of different APC subpopulations in periodontal disease.

Interleukin 15 skews monocyte differentiation into dendritic cells with features of Langerhans cells.

Langerhans cells (LCs) represent a subset of immature dendritic cells (DCs) specifically localized in the epidermis and other mucosal epithelia. As surrounding keratinocytes can produce interleukin (IL)-15, a cytokine that utilizes IL-2Rgamma chain, we analyzed whether IL-15 could skew monocyte differentiation into LCs. Monocytes cultured for 6 d with granulocyte/macrophage colony-stimulating factor (GM-CSF) and IL-15 differentiate into CD1a(+)HLA-DR(+)CD14(-)DCs (IL15-DCs). Agents such as lipopolysaccharide (LPS), tumor necrosis factor (TNF)alpha, and CD40L induce maturation of IL15-DCs to CD83(+), DC-LAMP(+) cells. IL15-DCs are potent antigen-presenting cells able to induce the primary (mixed lymphocyte reaction [MLR]) and secondary (recall responses to flu-matrix peptide) immune responses. As opposed to cultures made with GM-CSF/IL-4 (IL4-DCs), a proportion of IL15-DCs expresses LC markers: E-Cadherin, Langerin, and CC chemokine receptor (CCR)6. Accordingly, IL15-DCs, but not IL4-DCs, migrate in response to macrophage inflammatory protein (MIP)-3alpha/CCL20. However, IL15-DCs cannot be qualified as "genuine" Langerhans cells because, despite the presence of the 43-kD Langerin, they do not express bona fide Birbeck granules. Thus, our results demonstrate a novel pathway in monocyte differentiation into dendritic cells.

CD40-CD40 ligand interactions in vivo regulate migration of antigen-bearing dendritic cells from the skin to draining lymph nodes.

Whereas CD40-CD40 ligand interactions are important for various dendritic cell (DC) functions in vitro, their in vivo relevance is unknown. We analyzed the DC status of CD40 ligand -/- mice using a contact hypersensitivity (CHS) model system that enables multiple functions of DCs to be assessed in vivo. Immunohistochemistry of skin sections revealed no differences in terms of numbers and morphology of dendritic epidermal Langerhans cells (LCs) in unsensitized CD40 ligand -/- mice as compared with wild-type C57BL/6 mice. However, after contact sensitization of CD40 ligand -/- mice, LCs failed to migrate out of the skin and substantially fewer DCs accumulated in draining lymph nodes (DLNs). Furthermore, very few antigen-bearing DCs could be detected in the paracortical region of lymph nodes draining sensitized skin. This defect in DC migration after hapten sensitization was associated with defective CHS responses and decreased cutaneous tumor necrosis factor (TNF)-alpha production and was corrected by injecting recombinant TNF-alpha or an agonistic anti-CD40 monoclonal antibody. Thus, CD40-CD40 ligand interactions in vivo regulate the migration of antigen-bearing DCs from the skin to DLNs via TNF-alpha production and play a vital role in the initiation of acquired T cell-mediated immunity.

In situ evidence that the population of Langerhans cells in normal human epidermis may be heterogeneous.

Epidermal Langerhans cells (LC) may occur in subsets with different phenotypic and functional characteristics. In this work give further evidence that the CD1a-positive LC population in the normal human epidermis may be heterogeneous. We found that one of our monoclonal antibodies (TE4B) to stratum corneum chymotryptic enzyme (SCCE) stained a population of dendritic cells in the normal epidermis in addition to high suprabasal keratinocytes. The staining of the dendritic cells was seen only when the biopsies had been fixed with formaldehyde and when the sections had been pretreated, either with proteolytic enzymes or with Triton X-100. The binding of the antibody was mediated through its antigen binding site, as it could be inhibited by adsorption with recombinant pro-SCCE. Experiments with double labelling showed that the TE4B-positive dendritic cells were also CD1a-positive. On the other hand, not all CD1a-positive cells were TE4B-positive. By means of confocal microscopy of double-labelled cells, the TE4B binding site could be localized intracellularly. SCCE-mRNA could be detected by in situ hybridization in high suprabasal keratinocytes only. A possible explanation may be that there is a subset of LC which have taken up SCCE secreted by high suprabasal keratinocytes. Alternatively, TE4B may bind to an epitope present in a subgroup of epidermal LC which cross-reacts immunologically with SCCE. It is suggested that the demonstrated heterogeneity of the population of LC in the normal epidermis should be taken into account in studies on the possible role of epidermal autoantigens in the development of immune-mediated skin diseases.

Immunophenotyping of human dendriform cells from the conjunctival epithelium.

PURPOSE: Conjunctival Langerhans cells are bone marrow-derived, antigen-presenting cells that play a major role in the immune response of the ocular surface, but they have as yet been little investigated, either functionally or phenotypically. This study was undertaken in impression cytology to provide an extended immunophenotype of human conjunctival dendriform cells. METHODS: Immunostaining procedures were used to seek for the expression of the following 30 membrane antigens related to the immune system, using dendriform cells obtained in conjunctival specimens from 80 normal subjects and 105 with chronic conjunctivitis: class II antigens HLADR and DQ, CD1a (T6) and CD5, which usually mark Langerhans cells, macrophage markers CD14, CD36 and CD63, various lymphocyte antigens (CD2, CD4 and CD8), receptor to interleukin 2 (CD25), adhesion molecules and integrins (CD11a, CD11b, CD11c, CD18, CD29, CD41, CD61), the selectin CD62, ICAM-1 (CD54), ICAM-3 (CD50) and ELAM-1, CD45RO, related to activation of immune cells, and its ligand CD22, receptors to immunoglobulins (CD23 and CD32) and complement (CD21), transferrin receptor CD71, tryptase and vimentin, were thus investigated. RESULTS: Conjunctival dendriform cells reliably expressed several antigens: class II antigens HLA DR and HLA DQ, CD1a, vimentin, CD11a and CD18 (LFA-1), CD14, CD22, CD36, CD45RO, ICAM-3 and CD63. Other markers were only occasionally found (CD4, CD11b, CD29, CD32 and CD54), and the remaining above antigens were not expressed. No relevant difference was found between normal and inflammatory specimens in the immunophenotype of dendriform cells. CONCLUSIONS: This study sheds light on the main antigen-presenting cells of the ocular surface. The conjunctival cells share common immunophenotypic features with those from skin or mucosae, but our results showed some discrepancies, probably related to the specific immune status of the ocular structures.

[Immunophenotype of dendritic cells of the human conjunctiva]. / Immunophénotype des cellules dendritiques de la conjonctive humaine.

PURPOSE: To examine dendritic cells from human conjunctiva and to characterize their surface markers immunologically. METHODS: Conjunctival cells were isolated by conjunctival impression cytology from 150 patients: controls (65 patients, 126 eyes) or with various chronic inflammatory conditions (85 patients, 160 eyes); and by conjunctival biopsies from 25 patients: controls (10 patients) or treated topically for primary open angle glaucoma (15 patients). Immunostaining was performed using antibodies to investigate expression of 21 different membrane markers relevant to immunologic functions of dendritic cells. RESULTS: Conjunctival dendritic cells exhibited surface markers both in normal and inflammatory conditions: class II antigens HLA-DR and HLA-DQ, CD1a, vimentin, CD11a and CD18 (LFA-1), CD22, CD45RO and CD50. Some markers were more occasionally found CD4, CD11b, CD29, CD32, CD45RA and CD54, others being almost totally absent. Conjunctival inflammation induced the migration of dendritic cells from the stroma to the epithelium and thus increased their density. CONCLUSION: We conclude that conjunctival dendritic cells show common immunophenotypic features with those of other nonlymphoid tissues. Thus, conjunctival dendritic cells may be important in the immune regulation of the anterior segment.

Flow cytometric analysis and sorting of HLA-DR+CD1+ Langerhans cells.

There is a considerable need for reliable methods for enumeration and enrichment of Langerhans cells (LCs), since they continue to be the subject of intensive investigation in normal and diseased skin. It has been claimed that standard labelling with either anti-HLA-DR or OKT6 antibodies alone may fail to identify potentially important subsets of LCs with the phenotypes HLA-DR+CD1- and HLA-DR-CD1+. We report here on flow cytometric analysis of suction blister-derived normal epidermal cell (EC) suspensions, double stained with phycoerythrin-conjugated anti-HLA-DR and fluoresceinated OKT6. In seven separate experiments, no evidence for the existence of either HLA-DR+CDI- or HLA-DR-CDI+ ECs was obtained. We found that HLA-DR+CDI+LCs, which constituted a mean of 2.5% (+/- 0.3 SEM) of all ECs, could be readily identified on the basis of fluorescence, and that their light scatter characteristics were those of moderately sized cells of low granularity. We further describe our method for flow cytometric enrichment of such HLA-DR+CDi+ LCs for functional studies, based on selection on both fluorescence and light scatter criteria. Enrichment is to greater than 90% purity, and the method is applicable to the small number of ECs (approximately 1 x 10(6] obtained from a suction blister.

Rapid recovery of Langerhans cell alloreactivity, without induction of autoreactivity, after in vivo ultraviolet A, but not ultraviolet B exposure of human skin.

For therapeutic medical, cosmetic, and recreational reasons, humans expose themselves to increasing amounts of UVA. However, little is known of the photobiologic events associated with cutaneous carcinogenesis and photoaging that occur as a result of UVA exposure. UVB exposure of human skin abrogates the function of epidermal CD1+DR+ Langerhans cells and induces the appearance of CD1-DR+ non-Langerhans cell APC. This non-Langerhans cell APC population activates autoreactive immunoregulatory T cells that lead to suppressor-effector T cell function. In this report we show that, similarly to UBV, UVA exposure abrogates the function of CD1+DR+ Langerhans cells. However, in contrast to UVB, there is rapid recovery of Langerhans cell antigen-presenting cell activity and that CD1-DR+ non-Langerhans cell APC failed to appear to a significant degree. In keeping with the lack of CD1-DR+ epidermal cells, UVA exposed epidermal cells harvested 3 days after exposure functioned similarly to normal epidermis in that they activated alloreactive T cells but not autoreactive T cells in the absence of added Ag. This was in contrast to UVB irradiated epidermal cells that potently activate autoreactive T cells and contain CD1-DR+ cells. Thus, although both UVA and UVB initially depletes and inactivates CD1+DR+ Langerhans cells, the subsequent APC function of epidermal cells exposed to UVA differ profoundly from that of cells exposed to UVB. UVA radiation is less carcinogenic than UVB; differences in host responses to UV tumors may be linked to the rapid recovery of Langerhans cell function and the lack of induction of CD1-DR+ non-Langerhans cell APC after UVA exposure.

Quantification of T6+ and HLA/DR+ Langerhans cells in normal and inflamed human gingiva.

Langerhans cells are dendritic non epithelial cells found in the gingiva. The latest research in immunohistochemistry suggests that they may play an important role in the cellular immune response. The purpose of this quantitative study was to evaluate the number of Langerhans cells in association with gingival inflammation and the use of monoclonal antibodies reacting with two different antigens: T6 and HLA-DR, present on the cell membrane. Results indicate that Langerhans cells are mostly T6+; but HLA-DR appears as a good functional marker. Langerhans cells may play an important role in the cellular immune response to bacterial antigens in moderate inflammation of the gingiva.

Culture of putative Langerhans cell bone marrow precursors: characterization of their phenotype.

We searched for the presence of human CD1-positive cells in bone marrow populations in order to characterize putative Langerhans cell precursors. Bone marrow progenitors were cultured in 0.8% methylcellulose supplemented with 10% granulocyte-macrophage (GM) colony-stimulating factor(s) GCT and HTB9. We compared the kinetics of these two factors and found that GCT was the more appropriate for our study. After 8 days of culture, colony-forming units of granulocyte-macrophages (CFU-GM) were tested for the presence of CD1-positive cells using the immunofluorescence technique. Positive cells were counted by cytofluorometric analysis: 9.4% CD1a (BL6), 13.4% CD1c (L161), 4.3% CD1b (NuT2), 4.6% CD2 (T11), and 25.5% CD33 (My9). Ultrastructural features and phenotype were then specified by the immunogold labeling technique using electron microscopy. A subpopulation of CD1-positive cells showed the ultrastructural morphology of bone marrow pro-monocyte/monocyte cells. By using well-characterized monoclonal antibodies, it was demonstrated that these cells expressed the following phenotype: CD14+, CD33+, CD4+, HLA-DR+, HLA-DP+, HLA-DQ-, OKT10-, CD2-. These data indicate that these bone marrow promonocyte/monocyte progenitors express a phenotype similar to that of epidermal Langerhans cells but the density of each antigen is much lower than that observed on mature skin dendritic cells.

Interleukin-1 modulates T6 expression on a putative intra-epithelial Langerhans cell precursor population.

T6 is an antigen which is a highly specific marker for Langerhans cells. Previous studies have demonstrated that Interleukin-1 (IL-1) and an IL-1 inhibitor (ILS) modulate T6 expression (T6E) in explant culture. The present study examined the effects of IL-1 and ILS on T6E in dispersed gingival epithelial cell (EC) cultures. EC were obtained by trypsinization of gingival fragments obtained during periodontal surgery. T6E by EC was demonstrated using OKT6 monoclonal antibody in an immuno-peroxidase technique. In both unseparated and T6-depleted EC, IL-1 (0.5 U/mL) stimulated T6E, and this effect was abrogated by ILS (1:30). ILS alone depressed T6E in unseparated EC cultures. All effects were consistent between four- and 24-hour culture periods, and no treatment affected EC viability, thus excluding cell proliferation or necrosis as a vector for the action of IL-1 and ILS. These results indicate that a population of epithelial cells exists which is induced to express T6 under the influence of IL-1. IL-1 and ILS act in combination to regulate T6E on these precursor cells and on DR(-) Langerhans cells in gingival epithelium.

Effects of physicochemical agents on murine epidermal Langerhans cells and Thy-1-positive dendritic epidermal cells.

The possibility that Thy-1-positive dendritic epidermal cells (Thy-1+DEC) may contribute to the immunologic functions of murine epidermal cells (EC) prompted us to simultaneously assess the effects of certain immunomodulating physicochemical agents on both Thy-1+DEC and Ia-bearing Langerhans cells (LC). C3H/He mice received one of the following treatment modalities: UV-B irradiation (four consecutive days); psoralen plus UV-A (PUVA; three times a week for three consecutive weeks); topically and systemically applied glucocorticosteroids (GCS). Beginning 2 days after the last treatment, animals were sacrificed and the structure and surface marker expression of Ia+EC and Thy-1+DEC were assessed by immunohistologic means on epidermal sheet preparations from ear skin by using appropriate monoclonal antibodies. Whereas low-dose UV-B irradiation (4 X 100 or 200 J/m2) had little, if any, effect on either Ia+EC or Thy-1+DEC, high-dose UV-B (4 X 700 or 1000 J/m2) or PUVA treatment led to an almost complete disappearance of both surface characteristics. Immunoelectron microscopic studies revealed that in the case of LC, high-dose UV-B or PUVA treatment results in the disappearance of their anti-Ia reactivity but leaves their ultrastructural morphology intact. In sharp contrast, Thy-1+DEC escape ultrastructural detection after PUVA treatment and are greatly reduced in number after high-dose UV-B. Ia+EC continuously reappeared with both treatment modalities over a course of 4 to 6 wk, whereas even after 14 to 22 wk Thy-1+DEC were present only in negligible numbers. Similar to high-dose UV-B or PUVA therapy, administration of GCS resulted in the disappearance of both anti-Thy-1- and anti-Ia-reactive cells. Ultrastructural studies disclosed, however, that these steroid-induced alterations in the surface characteristics were accompanied by a dramatic reduction of the LC population but were not paralleled by morphologic changes of Thy-1+DEC. In the course of 7 wk after cessation of steroid treatment, the number of both Ia+EC and Thy-1+DEC had returned to normal values. The selective removal of either of these two dendritic epidermal cell populations by physicochemical agents may provide an excellent strategy to further clarify the functional properties of both LC and Thy-1+DEC.

Lymphomatoid papulosis. Characterization of skin infiltrates by monoclonal antibodies.

Cryostat sections from fully developed papular lesions of lymphomatoid papulosis (histologic subtype A or B) have been examined by immunoenzymatic staining with 24 monoclonal antibodies against lymphoid cells and their subsets. The lesions demonstrated essentially identical cellular compositions and consisted of T-lymphocytes with a peripheral phenotype (Lyt3+, anti-Leu-4+, OKT6-), macrophages (HLA-DR+, EB11+, OKM1+), and Langerhans cells (HLA-DR+, OKT6+). T-helper/inducer cells (anti-Leu-3+) usually dominated over T-suppressor/cytotoxic cells (anti-Leu-2+). In all cases, proportions of the infiltrating T-cells expressed markers associated with activation (HLA-DR, the OKT1O antigen, interleukin-2 receptor) or proliferation (transferrin receptor, the Ki-67 antigen) of lymphoid cells. Furthermore, the infiltrates contained clusters and/or sheets of large cells reactive with antibodies (Ki-1, Ki-24, Ki-27), which recognize Hodgkin's and Reed-Sternberg cells. These data indicate an origin of the cellular infiltrate from transformed or activated lymphoid cells and suggest an interrelationship of lymphomatoid papulosis to Hodgkin's disease.