Hyperstimulatory CD1a+CD1b+CD36+ Langerhans cells are responsible for increased autologous T lymphocyte reactivity to lesional epidermal cells of patients with atopic dermatitis.

We studied whether abnormalities in epidermal APC could be responsible for intracutaneous T cell activation in atopic dermatitis (AD). In the absence of added Ag, patients' peripheral blood T cells demonstrated significantly increased proliferation to their autologous lesional epidermal cells (mean +/- SEM = 19,726 +/- 9,754 cpm [3H]TdR uptake) relative to epidermal cells from uninvolved AD skin (2179 +/- 697 cpm) (n = 10) (p = 0.0001, log transformed data). AD T cell proliferative responses to autologous epidermal cells were dependent upon cells expressing HLA-DR, CD1a, and CD36, and not upon keratinocytes or their cytokines. Ultrastructurally, these cells ranged from typical Langerhans cells to indeterminate cells with irregular nuclear contours. Enriched populations of lesional AD Langerhans cells were highly stimulatory for autologous T cells, whereas equal numbers of Langerhans cells from non atopic epidermis were poor stimulators, even at high concentrations. The dermal perivascular dendritic cell markers CD36 and CD1b, not usually present on normal epidermal APC, were expressed by 40 and 60% of lesional AD CD1a+ epidermal Langerhans cells, respectively. Addition of anti-CD1b to cocultures of AD epidermal cells and autologous T lymphocytes augmented T cell activation, suggesting that the expression of CD1b by AD Langerhans cells may represent over expression of a molecule functionally linked to the enhanced T cell stimulatory capacity of these cells. Thus, stimulatory signals for T cells contained within AD epidermis are carried by cells in an abnormal differentiation state as indicated by expression of phenotypic characteristics of both epidermal and dermal antigen presenting cells (HLA-DR+, CD1a+, CD1b+, CD36+). We propose that activation of autologous T cells by an altered cutaneous APC population may represent a mechanism for the hyperactive and disordered cell-mediated immune response that characterizes the dermatitic lesions of AD.     

Detection of distinct subpopulations of Langerhans cells by flow cytometry and sorting

Flow cytometry was found to be a very appropriate tool for the study of Langerhans cells (LC), which represent a minor cell population (2-3%) of human epidermis, and allowed us to obtain new phenotypic, functional, and cell cycle data on these rare cells. The phenotypic analysis of cell surface antigens demonstrates the existence of two subpopulations of LC: the former is HLA-DR+ and OKT 6+ (about 90% of total HLA-DR+ cells) and the latter is HLA-DR+ and OKT 6- (about 10% of total HLA-DR+ cells). These subpopulations of LC are both able to stimulate the proliferation of peripheral blood lymphocytes (PBL) in the presence of keratinocytes i.e., in mixed skin lymphocyte reaction (MSLR). Analysis of the cell cycle could be performed on OKT 6+ LC. Results show that they can be found in the various phases of the cell cycle, suggesting that the large majority of Langerhans cells are able to proliferate in situ in normal human epidermis.     

Characterization of adult human marrow hematopoietic progenitors highly enriched by two-color cell sorting with My10 and major histocompatibility class II monoclonal antibodies

Monoclonal antibodies, My10 (HPCA-1) and major histocompatibility class II (HLA-DR), were used to enrich and phenotype normal human marrow colony-forming unit: granulocyte-macrophage (CFU-GM), burst-forming unit: erythroid (BFU-E), and multipotential colony-forming unit: granulocyte-erythroid-macrophage-megakaryocyte (CFU-GEMM) progenitor cells. Nonadherent low density T lymphocyte-depleted marrow cells were sorted on a Coulter Epics 753 dye laser flow cytometry system with the use of Texas Red-labeled anti-My10 and phycoerythrin conjugated anti-HLA-DR. Cells were separated into populations with nondetectable expression of antigens (DR-My10-) or with constant expression of one antigen and increasing densities of the other antigen. More than 98% of the CFU-GM, BFU-E, and CFU-GEMM were found in fractions containing cells expressing both HLA-DR and My10 antigens. The cloning efficiency (CE) of cells in the DR-My10- cell fraction was 0.01%. In the antigen-positive sorted fractions, the CE was highest (up to 47%) in the fractions of cells expressing high My10 and low DR (My10 DR+) antigens and was lowest (2.5%) in the fraction of cells expressing low My10 and low DR (My10+DR+) antigens. Populations of cells varying in the density of HLA-DR, but not My10, antigens varied in the proportion and types of progenitor cells present. When My10-positive cells were sorted for HLA-DR density expression, the CE for CFU-GM was similar in the DR+ and DR++ fractions, but most of the BFU-E and CFU-GEMM were found in the DR+ fraction. Within the CFU-GM compartment, most of the eosinophil progenitors were found in the DR+ fraction, whereas a greater proportion of macrophage progenitors were detected in the DR++ fraction. CFU-GM and BFU-E in the fractions of cells positive for DR and My10 were assessed for responsiveness to the effects of recombinant human tumor necrosis factor-alpha, recombinant human interferon-gamma, and prostaglandin E1. Colony formation from CFU-GM was suppressed by the three molecules, and colony formation by BFU-E was suppressed by recombinant human tumor necrosis factor-alpha and interferon-gamma and enhanced, in the presence of T lymphocyte-conditioned medium, by prostaglandin E1 in all antigen-positive fractions.(ABSTRACT TRUNCATED AT 400 WORDS)     

Targeting of HLA-DR molecules transduces agonistic functional signals in cutaneous melanoma

The role of human leukocyte antigens (HLA) class II molecules in transducing intracellular signals in immune cells is well established. Solid tumors of different histotype can also express HLA class II antigens; however, their intracellular signaling ability is essentially unknown. Due to the frequent expression of HLA class II molecules in primary and metastatic lesions, cutaneous melanoma was utilized to investigate whether the engagement of HLA-DR molecules transduces functional intracellular signal(s). Triggering of HLA-DR molecules by the anti-HLA-DR monoclonal antibody (mAb) L243 induced a significant (P < 0.05) and dose-dependent growth-inhibition of metastatic melanoma cells Mel 120, as well as their homotypic aggregation. Furthermore, an increase in tyrosine phosphorylation of multiple cellular proteins with a molecular weight ranging from 66 to 130 kD, including p125 focal adhesion kinase, was observed. Lastly, the engagement of HLA-DR molecules by mAb L243 inhibited activator protein-1-DNA binding. Thus, HLA-DR molecules expressed on melanoma cells can transduce functional intracellular signals. This finding is consistent with evidences obtained in hematological malignancies, and suggests the potential usefulness of HLA-DR molecules to set-up new approaches of targeted therapy in metastatic melanoma.     

Chemokines and chemokine receptors expression in the lesions of patients with American cutaneous leishmaniasis

American cutaneous leishmaniasis (ACL) presents distinct active clinical forms with different grades of severity, known as localised (LCL), intermediate (ICL) and diffuse (DCL) cutaneous leishmaniasis. LCL and DCL are associated with a polarised T-helper (Th)1 and Th2 immune response, respectively, whereas ICL, or chronic cutaneous leishmaniasis, is associated with an exacerbated immune response and a mixed cytokine expression profile. Chemokines and chemokine receptors are involved in cellular migration and are critical in the inflammatory response. Therefore, we evaluated the expression of the chemokines CXCL10, CCL4, CCL8, CCL11 and CXCL8 and the chemokine receptors CCR3, CXCR3, CCR5 and CCR7 in the lesions of patients with different clinical forms of ACL using immunohistochemistry. LCL patients exhibited a high density of CXCL10+, CCL4+ and CCL8+ cells, indicating an important role for these chemokines in the local Th1 immune response and the migration of CXCR3+ cells. LCL patients showed a higher density of CCR7+ cells than ICL or DCL patients, suggesting major dendritic cell (DC) migration to lymph nodes. Furthermore, DCL was associated with low expression levels of Th1-associated chemokines and CCL11+ epidermal DCs, which contribute to the recruitment of CCR3+ cells. Our findings also suggest an important role for epidermal cells in the induction of skin immune responses through the production of chemokines, such as CXCL10, by keratinocytes.     

Cell surface expression of invariant gamma-chain of class II histocompatibility antigens in human skin

A rat monoclonal antibody (McAb 21:9) reactive with the human invariant gamma-chain of class II major histocompatibility complex (MHC)-encoded antigens was isolated and was shown to react with the carbohydrate-carrying, COOH-terminal part of the gamma-chain. The McAb 21:9 binds to a molecule that is identified as the gamma-chain for the following reasons: it has an apparent m.w. of 33,000, similar to that of the gamma-chain; it has a two-dimensional gel migration pattern identical to that of the gamma-chain; and it associates with immature, but not processed class II antigens. When used for immunohistochemical staining on sections of normal human skin, only dendritic, class II MHC antigen, and anti-Leu-6 reactive Langerhans cells are labeled in the epidermis. HLA-DR-expressing keratinocytes present in the tuberculin reaction, cutaneous T cell lymphoma, and lichen planus, however, did not react with the anti-gamma-chain antibody, nor with a HLA-DQ-reactive antibody. Cell surface expression of the gamma-chain was observed on 1 to 3% of normal viable epidermal cells in suspension. By using double indirect immunofluorescence, it was possible to demonstrate the simultaneous binding of anti-gamma-chain, anti-HLA-DR, anti-Leu-10, and anti-Leu-6 antibodies, respectively, on the same cells, thus confirming their identity as Langerhans cells. The presence of the gamma-chain on the surface of the immunocompetent Langerhans cells may indicate that the cell surface, not the cytoplasm as has been suggested, is the site of the primary function of the gamma-chain.     

DR antigen expression on ovarian carcinoma cells does not correlate with their capacity to elicit an autologous proliferative response

Summary Expression of HLA-DR antigens by purified preparations of human ovarian carcinoma cells freshly isolated from surgical specimens was examined in parallel with the capacity of tumor cells to elicit a blastogenic response from autologous lymphocytes in mixed lymphocyte-tumor culture (MLTC) assay. Of 21 tumor preparations, 11 (52%) reacted with monoclonal antibodies 279 and/or 949 specific for a monomorphic determinant of HLA-DR antigens, with heterogeneous positivity, ranging between 30% and 95%. In this series of patients positive MLTC occurred in 8/21 individual experiments. The HLA-DR expression was proportionally similar in tumors giving positive MLTC (4/8=50%) and negative MLTC (7/13=53%). The lack of correlation between DR expression on tumor cells and stimulatory activity in autologous MLTC and the fact that DR-negative tumors could induce lymphocyte stimulation, support the hypothesis that blastogenesis occurs upon recognition of tumor-associated antigens, different from DR molecules, possibly tumor-specific antigens.     

Expression of HLA-DR, MB, MT and SB antigens on human mononuclear cells: identification of two phenotypically distinct monocyte populations

The expression of HLA-DR, SB, MB, and MT antigens in different populations of human mononuclear cells was investigated with the use of monoclonal antibodies that recognize distinct human Ia-like antigens. Our results indicate that in man, as previously reported in other species, two phenotypically distinct populations of monocytes or macrophages can be identified on the basis of expression of Class II MHC antigens. Virtually all circulating monocytes displayed determinants associated with HLA-DR, SB, and MT. In addition, a subpopulation of human monocytes expressed MB/DS-associated antigens, as detected with monoclonal antibodies specific for MB1, MB3, and DS-framework determinants. Most B lymphocytes expressed antigens associated with HLA-DR, and the specificities SB2, SB3, MB1, MB3, MT2, and MT3 were also present. Resting T lymphocytes were unreactive with antibodies that recognize all of the Class II MHC antigens tested. T lymphocytes activated by soluble antigen or alloantigens, and expanded in culture, expressed DR, SB, MB, and MT. The majority of the MB/DS+ cells present in the adherent population were monocytes, because they were phagocytic and had the monocyte-specific marker 63D3. The rest of the cells were not identified. They are likely to include mostly B lymphocytes. The presence of other cells, such as dendritic cells, in this subset needs to be determined.     

BCG immunotherapy in stage I melanoma patients

Summary Previously, we have provided evidence for a positive correlation between HLA-DR expression in primary melanoma and early metastasis [3, 4]. In the present study we investigated whether this relationship was modified by adjuvant BCG immunotherapy. The study comprised 107 patients with a stage I high-risk melanoma; 44 patients had been treated with BCG, whereas the remaining patients had not received any adjuvant therapy. There was no difference in disease-free survival between BCG-treated and untreated patients. Disease-free survival was significantly shorter in patients with high expression of HLA-DR antigens in the primary tumor.Subgrouping BCG-treated and control patients according to HLA-DR phenotype of the melanoma revealed a prolongation of disease-free survival in the subgroup of BCG-treated patients with no or low expression of HLA-DR antigens in the primary melanoma. BCG therapy apparently did not influence prognosis of patients with high expression of HLA-DR antigens in the tumor.     

Correlation between keratinocyte expression of Ia and the intensity and duration of contact hypersensitivity responses in mice

Langerhans cells are the only cells within the epidermis that normally express immune response-associated antigens (referred to as Ia in mice and HLA-D in humans). However, in the epidermis of patients with allergic contact dermatitis or individuals undergoing a delayed-type hypersensitivity response, the keratinocytes at the reaction site are induced to express HLA-DR. In this study the inducible expression of Ia by the keratinocytes of mice was found to be directly correlated with the intensity and duration of experimentally induced contact hypersensitivity (CH) responses. During a CH response in animals that were sensitized on the belly and challenged on the ear with the contact-sensitizing (CS) agent oxazolone, the keratinocytes in the challenged, but not the unchallenged, ear were induced to express Ia. In comparison with animals that were sensitized and challenged at different sites, an intensified expression of Ia by the keratinocytes was associated with a twofold increase in ear swelling in mice that were sensitized and challenged with oxazolone at the same site. Curiously, the challenge of oxazolone-sensitized ears with dinitrofluorobenzene (an unrelated CS agent), croton oil (a nonspecific inflammatory agent), or acetone/olive oil (a noninflammatory agent) also induced both a marked keratinocyte expression of Ia and an enhanced CH response. These results suggest that residual antigen at the original sensitization site may be mobilized to function as the challenge stimulus to elicit a CH response, in association with keratinocyte expression of Ia, when CS-sensitized skin is perturbed with a nonspecific agent. Further evidence of an association between CH responsiveness and keratinocyte expression of Ia came from the following observations. First, the magnitude and duration of a CH response was markedly increased in pertussis toxin (PT)-treated mice. These enhanced responses were associated with intense Ia expression by the keratinocytes in the epidermis at the reaction site. Because PT is known to have an adjuvant effect on delayed-type hypersensitivity reactions, as well as to alter the normal regulatory mechanisms associated with this type of response, it is possible that Ia+ keratinocytes play a synergistic role in the enhanced CH responses that are observed in PT-treated animals. Second, a direct correlation between keratinocyte expression of Ia and CH responsiveness was observed in athymic nude mice that were challenged with oxazolone after receiving an adoptive transfer of lymphoid cells from oxazolone-primed normal syngeneic donors.(ABSTRACT TRUNCATED AT 400 WORDS)     

Detection of HLA-DR associated PLT determinants by alloreactive lymphocyte clones

This study deals with alloreactive T-cell clones which recognize cellular determinants associated with HLA-DR antigens. Two clones, CB55 and DS56, exhibited a PLT specificity that was perfectly associated with DR5. On the other hand, clones CB7, DS1 and HS1 showed PLT reactivity with approximately one-half of the DR5 positive cells and none of the DR5 negative cells, whereas clone MD4 largely reacted with the other half of DR5 positive cells. Another MLR culture generated two alloreactive clones DS6 and DS9 with PLT specificity for DR2. However, these clones did not respond to DR2 cells, which were also positive for the DR2-associated HLA-B7 and B18 antigens. Monoclonal antibody (mAb) inhibition studies showed heterogenous patterns, whereby monomorphic non-DR mAbs inhibited the DR2-associated PLT clones while the DR5-associated PLT clones were inhibited by different groups of anti-DR and non-DR mAbs. These observations suggest the existence of several lymphocyte-activating determinants associated with HLA-DR antigens. This diversity may be an important consideration in studies of the role of HLA-DR in immune mechanisms and transplant compatibility.     

Interferon-gamma modulates HLA class II antigen expression on cultured human thymic epithelial cells

Cultures of human thymic epithelial cells (TEC) were tested for the expression of HLA class I (A, B, C) and class II (DR and DC) antigens by indirect immunofluorescence. The epithelial nature of the cells was proven by using an antikeratin antiserum. A high level of expression (close to 100% positive cells) of HLA class I antigens was observed on TEC at the beginning of the culture and remained unchanged for up to 12 days. In contrast, HLA class II antigen expression (85% DR+ and 75% DC+ cells on day 2) decreased gradually and reached very low levels (less than 5% DR+ or DC+) by day 7 of culture. This loss of class II antigen expression was not seen when cultures were performed in the presence of supernatants from activated T cells containing interferon-gamma (IFN-gamma). Furthermore, the presence of recombinant IFN-gamma (rIFN-gamma) in the medium from the onset of culture maintained HLA-DR and DC antigen expression on a high number of cells (comparable to that observed on day 2 of culture). A large percentage of rIFN-gamma-treated cells also showed intracytoplasmic HLA-DR antigen expression. Addition of rIFN-gamma at various times after the onset of the culture led to a reinduction of DR and DC antigen expression. This effect of rIFN-gamma was observed in 48 hr with concentrations as low as 10 IU/ml and was apparently specific for this IFN species, in that rIFN-alpha was unable to modify HLA class II antigen expression at concentrations up to 1000 IU/ml. The increased expression of HLA class II antigen was truly due to induction in individual TEC, rather than selection of class II-positive cells, because induction under the influence of IFN-gamma was reversible and occurred in the absence of proliferation in mitomycin-treated or gamma-irradiated cultures. Our results indicate that synthesis and membrane expression of class II HLA antigens are enhanced by IFN-gamma in TEC cultures. This finding raises the possibility that IFN-gamma participates in the mechanisms that assure the permanent expression of DR and DC antigens observed in TEC in vivo, with potentially important functional consequences in terms of education for self recognition.     

Antinuclear antibody-keratinocyte interactions in photosensitive cutaneous lupus erythematosus

Autoimmune diseases are characterized by various circulating autoantibodies, especially antinuclear antibodies (ANA). It has been a long-standing issue as to whether and/or how ANA interact with epidermal cells to produce skin lesions. Of these ANA, the anti-SS-A/Ro antibody is the most closely associated with photosensitivity in patients with systemic lupus erythematosus (SLE) and its subgroups, including subacute cutaneous lupus erythematosus (SCLE) and neonatal lupus erythematosus (NLE). SS-A/Ro antigens are present in the nucleus and cytoplasm, and interestingly, ultraviolet B (UVB) light translocates these antigens to the surface of the cultured keratinocytes. Thus, anti-SS-A/Ro antibodies in the sera can bind to the relevant antigens expressed on the UVB-irradiated keratinocyte surface, and have been speculated to be an important inducer of antibody-dependent keratinocyte damage. This interaction between the anti-SS-A/Ro antibodies and UVB-irradiated keratinocytes may induce the skin lesions through a cytotoxic mechanism. This review will focus on the involvement of antibody-dependent cellular cytotoxicity in the pathogenesis of the skin lesions observed in photosensitive cutaneous lupus erythematosus.     

Coumarin (1,2-benzopyrone) enhances DR and DQ antigen expressions by peripheral blood mononuclear cells in vitro.

Coumarin (1,2-benzopyrone) is a natural substance that appears to have some clinical activity against renal cell carcinoma and malignant melanoma. Preliminary evidence from in vitro and in vivo studies suggests that coumarin possesses immunomodulatory activity. It was reported previously that coumarin therapy resulted in augmented DR antigen expression by peripheral blood monocytes in cancer patients. The purpose of the present study was to examine the effects of coumarin on DR and DQ antigen expression by normal donor peripheral blood mononuclear cells in vitro. Using monoclonal antibody labeling techniques and FACS analysis, it was shown that both DR and DQ antigen expression by peripheral blood mononuclear cells were enhanced over controls after 48 hours of exposure to coumarin. While monocytes normally express these antigens, enhanced expression is consistent with an activated state. These results support the hypothesis that coumarin acts, at least in part, through immune augmentation.     

Characterization of cryopreserved human Langerhans cells

Epidermal Langerhans cells are potent antigen-presenting cells in the epidermis. The establishment of a cryopreservation method for human Langerhans cells would greatly contribute to our ability to successfully conduct various experiments dealing with Langerhans cells. Since Langerhans cells are known to be sensitive to cold injury, there have been no reports concerning the cryopreservation of Langerhans cells. We have investigated the effect of cryopreservation on the function and phenotype of human Langerhans cells. Langerhans cells from human foreskins were isolated with the immunomagnetic microbead method using monoclonal antibodies for CD1a. Langerhans cells were cryopreserved in the presence of dimethylsulfoxide (DMSO) 10% and fetal calf serum 90%. Cryopreserved Langerhans cells were phenotypically assessed by flowcytometry using monoclonal antibodies to HLA-DR and CD1a. The ultrastructures of the Langerhans cells were compared using electron microscopy. An autologous T cell stimulation test was performed to compare the functions of cryopreserved Langerhans cells and fresh Langerhans cells. The viability of the cryopreserved Langerhans cells was able to be maintained at more than 90%. Cryopreserved Langerhans cells expressed high levels of HLA-DR and CD1a antigens and stimulated autologous T cells to an extent almost identical to that obtained from fresh Langerhans cells. These findings indicate that the cryopreservation of human Langerhans cells could lead to a breakthrough in various experiments dealing with human Langerhans cells.     

In vivo treatment with anti-I-A antibodies: differential effects on Ia antigens and antigen-presenting cell function of spleen cells and epidermal Langerhans cells

The in vivo activation of T cells by a variety of antigens can be inhibited by the administration of anti-I-A antibodies (Ab) at the time of antigen priming. This inhibition can partially be explained by the temporary loss of Ia molecules from Ia-bearing antigen-presenting cells (APC) in the spleen. In this study, the effects of i.p. injected monoclonal Ab specific for I-A glycoproteins of different H-2 haplotypes on Ia antigen expression and APC function of spleen cells and epidermal Langerhans cells were compared. It was found that anti-I-A Ab quickly bound to both spleen cell and Langerhans cell Ia antigens. Although spleen cell Ia antigens were modulated and thus temporarily disappeared, Ia antigen expression by epidermal Langerhans cells was not modulated. In functional studies, the capacity of spleen cells and epidermal cells from anti-I-A Ab treated vs control animals to function as APC for antigen-specific, I-A- or I-E-restricted T cell clones was tested. A single injection of anti-I-A Ab completely abolished the APC function of spleen cells as shown in several inbred mouse strains, F1 animals, and with the use of several different Ab and T cell clones. In contrast, Langerhans cell-dependent APC function of epidermal cells remained completely unaltered. Even multiple injections of high doses of Ab never caused any inhibition of Langerhans cell function. Experiments with anti-I-Ak or anti-I-Ad Ab in an (H-2k X H-2d)F1 animal showed abrogation of APC function of spleen cells, but again not of Langerhans cells. Thus in vivo anti-I-A Ab administration appears to differentially affect Ia antigen expression and APC function from spleen and epidermis: Ia antigens are modulated from spleen cells but not from epidermis, and APC function disappears in the spleen but not in the epidermis. The abrogation of splenic but not of Langerhans cell APC function with anti-I-A Ab will facilitate the dissection of the relative contributions of Langerhans cells as compared with other APC in the generation of cutaneous immune responses.     

In vitro and in situ expression of IL-23 by keratinocytes in healthy skin and psoriasis lesions: enhanced expression in psoriatic skin

Keratinocytes contribute to cutaneous immune responses through the expression of cytokines. We investigated whether human keratinocytes can express IL-23, a newly defined IFN-gamma-inducing cytokine composed of a unique p19 subunit and a p40 subunit shared with IL-12. Cultured keratinocytes from normal and lesional psoriatic skin were found to express constitutively mRNA for both subunits of IL-23. Low but significant levels of the heterodimeric IL-23 protein could be detected in cell lysates and supernatants from stimulated keratinocytes by immunoblotting and ELISA. Functional analysis showed that these low levels of keratinocyte-derived IL-23 were sufficient to enhance the IFN-gamma production by memory T cells. Immunostaining of skin sections confirmed expression of both subunits of IL-23 by keratinocytes in situ and also revealed expression of this cytokine in the dermal compartment. IL-23 expression was significantly higher in psoriatic lesional skin, compared with normal and psoriatic nonlesional skin. The immunostained preparations of cultured cells and IL-23 levels in culture supernatants did not show any difference between normal and psoriatic keratinocytes indicating no intrinsic aberration of IL-23 expression in keratinocytes from psoriatic skin. Double staining of cytospin preparations demonstrated that IL-23 p19 is also expressed by epidermal Langerhans cells, dermal dendritic cells, and macrophages. Psoriasis is a chronic inflammatory skin disease mediated by IFN-gamma-expressing type 1 memory T cells. As IL-23 is important to activate memory T cells to produce IFN-gamma, its augmented expression of IL-23 by keratinocytes and cutaneous APC may contribute to the perpetuation of the inflammation process in this disease.     

Changes in the number and distribution of Langerhans cells in the hydantoin hyperplasic gingiva as compared with the clinically normal one.

A study was made of the number of Langerhan's cells (LCs) per mm2 of section which express the antigens T6 and/or HLA-DR in seriated gingival sections of diphenylhydantoine-induced hyperplasia (HG) and clinically normal gingivae (NG). NG showed histological correlation with its macroscopic appearance. In HG the classical histopathological findings were verified, as well as the epithelial maturation irregularities, conductive to the development of epithelial gaps. In the immunostained samples, LCs appear amply distributed in the epithelium in greater numbers than in NG and more branched except in the immature areas, where they mostly express HLA-DR. In HG keratinocytes, HLA-DR+ are observed in the basal layer, except in developing epithelial gap zones. The Wilcoxon test for the NG-T6/NG-DR and HG-T6/HG-DR was not significant; but the Mann Whitney test for NG-T6/HG-T6 and NG-DR/HG-DR was significant to p less than 0.05. It is understood that the increase in LC numbers in HG is a manifestation of their active participation in local immune reactions. The presence of DR+/T6- LCs in the less keratinized areas seems to indicate the relationship of LCs with epithelial proliferation and/or differentiation.     

Cell populations in lesions of cutaneous leishmaniasis of Leishmania (L.) amazonensis- infected rhesus macaques, Macaca mulatta

The cellular nature of the infiltrate in cutaneous lesion of rhesus monkeys experimentally infected with Leishmania (L.) amazonensis was characterized by immunohistochemistry. Skin biopsies from infected animals with active or healing lesions were compared to non-infected controls (three of each type) to quantitate inflammatory cell types. Inflammatory cells (composed of a mixture of T lymphocyte subpopulations, macrophages and a small number of natural killer cells and granulocytes) were more numerous in active lesions than in healing ones. T-cells accounted for 44.7 +/- 13.1% of the infiltrate in active lesions (versus CD2+ = 40.3 +/- 5.7% in healing lesions) and T-cell ratios favor CD8+ cells in both lesion types. The percentage of cells expressing class II antigen (HLA-DR+) in active lesions (95 +/- 7.1%) was significantly higher (P < 0.005) from the healing lesions (42.7 +/- 12.7%). Moreover, the expression of the activation molecules CD25 (@ 16%), the receptor for interleukin-2, suggests that many T cells are primed and proliferating in active lesions. Distinct histopathological patterns were observed in lesions at biopsy, but healing lesions contained more organized epithelioid granulomas and activated macrophages, followed by fibrotic substitution. The progression and resolution of skin lesions appears to be very similar to that observed in humans, confirming the potential for this to be used as a viable model to study the immune response in human cutaneous leishmaniasis.