Normal Langerhans Cells Research Articles

Langerhans' cell histiocytosis cells are activated Langerhans' cells.

Langerhans' cell histiocytosis (LCH) is characterized by the presence of large mononucleated cells, associated with inflammatory cells. The Langerhans' cell (LC) lineage of the mononucleated cells is suggested by the presence of Birbeck granules and the expression of CD1a. We investigated the presence of 14 markers expressed by normal LCs in vitro. Nine skin and one lymph node frozen biopsies of LCH children were analysed by in situ immunohistochemistry. The data were compared with six skin and five lymph node frozen biopsies. LCH cells of the ten samples were positive for all 14 LC markers. We observed three different groups of markers, according to the respective staining of normal LCs and LCH cells. Group 1 included DR, DQ, CD1a, CD1c, and ICAM-3. Markers of group 1 were present on the majority of both normal LCs and LCH cells. Group 2 included CD1b, CD4, LFA-1, LFA-3, CD32, and CD68. Markers of group 2 were detected on the majority of LCH cells, but only on a fraction of normal LCs. Group 3 included CD11b, CD24, and B7/BB1. Markers of this group were detected on LCH cells, but not on normal LCs. This in situ immunohistochemical study confirms that LCH cells belong to the LC lineage. The different clinical LCH syndromes had the same immunohistochemical staining. The expression of some markers of groups 2 and 3 is known to be related to the activation of LCs in vitro. Our study suggests that LCH cells are activated LCs.

Opposing cytokine production by normal Langerhans cells (IL-12) and UV-induced macrophages (IL-10)

Opposing cytokine production by normal Langerhans cells (IL-12) and UV-induced macrophages (IL-10)

Neutrophils, Differentiated Macrophages, and Monocyte/Macrophage Antigen Presenting Cells Infiltrate Murine Epidermis After UV Injury

We asked whether, as in humans, a population of antigen-presenting macrophages infiltrates the epidermis of ultraviolet (UV)-exposed BALB/c mice. Using three-color flow cytometry on cell suspensions plus in situ immunofluorescence microscopy, the phenotype of normal Langerhans cells was class II major histocompatibility complex (MHC+), CD11b+, NLDC-145+, BM8+ CD45+ and homogeneous. By contrast, in epidermal cells harvested 3 d following UV (UV-EC), there were two subsets of class II MHC+ cells: 1) class II MHChi CD11b+, and 2) class II MHClo CD11b-. Neither expressed the Langerhans cell markers BM8 and NLDC-145. In addition, there were two major populations of class II MHC- CD11b+ cells; half of these expressed the GR-1 neutrophil marker. Langerhans and dendritic epidermal T cells were markedly reduced after UV injury. By electron microscopy, immunomagnetic bead-purified CD11b+ cells in UV-EC were comprised of neutrophils, differentiated macrophages, and mononuclear cells with prominent lysosomes, but no Birbeck granules; the class II MHC+ subset resembled a monocytic cell in between differentiated macrophages and indeterminate dendritic cells. Functionally, immediately following in vivo UV exposure, the allogeneic antigen-presenting cell capacity of UV-EC was reduced to 21 +/- 6% of control epidermal cells (C-EC); by 3 d, antigen-presenting cell activity of UV-EC had recovered to 59 +/- 11% of C-EC, although at this time NLDC-145+ Langerhans cells had reached their lowest number. The recovered antigen-presenting cell activity was critically dependent upon the class II MHChiCD11b+ cells. Sensitization of BALB/c mice through skin that contained these antigen-presenting cells (3 d after UV) resulted in tolerance to dinitrofluorobenzene. By contrast, sensitization through UV-exposed skin immediately after the exposure resulted in unresponsiveness without tolerance, demonstrating temporal association of tolerance with leukocytic infiltration. In summary, murine epidermis responds to an acute UV injury in vivo with an initial abrogation of antigen-presenting activity followed by epidermal infiltration with neutrophils, differentiated macrophages, and monocytic antigen-presenting cells that are distinct from Langerhans cells with regard to expression of Langerhans cell markers and ultrastructure.

Surface Phenotype of Langerhans Cells and Lymphocytes in Granulomatous Lesions from Patients with Pulmonary Histiocytosis X

Pulmonary histiocytosis X (HX) is a disorder characterized by the presence of granulomas in which Langerhans cells (LC) and lymphocytes are abundant. Although the pathogenesis of pulmonary HX remains unknown, an uncontrolled immune response initiated by LC, which are potent antigen-presenting cells in vitro, may play an important role. To further characterize LC and lymphocytes present in granulomas from these patients, we used immunohistochemical techniques and monoclonal antibodies to evaluate the surface phenotype and electron microscopy (EM) to seek evidence for close interactions between both cell types in these lesions. In all samples, HX granulomas contained large numbers of strongly positive CD1a cells in which typical Birbeck granules were identified by EM. The number of Birbeck granules in LC from HX granulomas was strikingly increased compared with that in LC in the bronchioles of normal subjects. Furthermore, unlike normal LC, essentially all LC in HX granulomas expressed CD4 antigens and were strongly positive for CD1c. Lymphocytes infiltrating HX granulomas were almost entirely CD3+ T cells and were mainly CD4 positive (CD4/CD8 ratio 3.7 +/- 1.3). These T lymphocytes expressed almost exclusively alpha/beta T cell receptors, and gamma/delta T cells were rarely observed (< 5% of CD3+ cells). In areas of lymphocytic infiltration, close differentiated contacts between LC and lymphocytes were observed by EM in all samples. These results demonstrate that interactions between activated LC and CD4+ T lymphocytes are prominent in early HX granulomas and support the idea that an immune response in which LC serve as accessory cells is involved in the pathogenesis of this disorder.

Regulation of the skin immune system by retinoids during carcinogenesis.

One of the immunosuppressive effects of both ultraviolet (UV) light and chemical carcinogens is to deplete Langerhans cells (LC) from the epidermis, suggesting that these cells play an important role in inducing immune responses to developing tumors during the early phases of carcinogenesis. Retinoids such as all-trans-retinoic acid (RA) are natural or synthetic derivatives of vitamin A; RA binds to nuclear receptors in the skin, effecting transcription of a wide range of genes. Topical application of RA prevents the tumor promotor 12-O-tetradecanoylphorbol-13-acetate (TPA) from depleting the density of LC in murine epidermis. In contrast, topical RA did not itself alter the normal LC density. RA also inhibited the development of TPA-induced immunosuppression to a locally applied contact sensitizer. Topical RA also prevented UV light from reducing the density of both LC and Thy-1+ dendritic epidermal cells (Thy-1+ dEC). However, the RA treatment did not prevent local immunosuppression to the contact sensitizer from developing in response to UV irradiation. The reasons for this are unclear, however, it is possible that RA does not inhibit some other immunosuppressive effect of UV light. Temarotene, a recently developed synthetic retinoid also inhibited UV light from reducing the LC and Thy-1+ dEC density from murine epidermis. Thus part of the anti-carcinogenic activity of retinoids may be due to their ability to protect LC during the early stages of carcinogenesis.

Dynamic nature and function of epidermal Langerhans cells in vivo and in vitro: a review, with emphasis on human Langerhans cells.

Epidermal Langerhans cells (LC) are Birbeck granule-containing bone-marrow-derived cells, which are located mainly in the suprabasal layer of the epidermis. They can be readily identified by their strong expression of CD1a and MHC class II molecules. In addition to these 'classical' properties, an extensive phenotypic profile of normal human LC, summarized in this review, is now available. The powerful capacity of LC to activate T lymphocytes is clearly documented and, to date, LC are recognized as the prominent antigen-presenting cells of the skin immune system. They are generally believed to pick up antigens encountered in the epidermis and to migrate subsequently from the epidermis to the skin-draining lymph nodes. Upon arrival in the paracortex of lymph nodes, the antigen-laden LC transform into interdigitating cells and they present antigen to naive T lymphocytes in a MHC class II-restricted fashion; this results in the generation of antigen-specific immune responses. It has also been demonstrated that transformation of LC into interdigitating cells occurs when LC are cultured in vitro. Both in vivo and in vitro studies have indicated that properties of LC, such as phenotype, morphology and the stimulatory potential to activate T lymphocytes, are dependent on the local microenvironment in which the LC reside. The essential role of LC in the induction of contact allergic skin reactions and skin transplant rejection is well established.

IgE-binding molecules on human Langerhans cells.

We have recently demonstrated that normal human Langerhans cells are able to bind IgE. The study of IgE-binding molecules on normal LC led to the characterization of three distinct structures able to bind IgE, viz. the low affinity receptor for IgE, Fc epsilon R2/CD23, the so-called IgE-binding protein epsilon BP which is the human homologous of the murine Mac-2 antigen, and finally the high affinity receptor for IgE, Fc epsilon RI. In this review, we summarize the most recent data on these structures and their putative physiological relevance is discussed with regard to the atopic disease.

In vivo Modulation of the High-Affinity Receptor for IgE (FcεRI) on Human Epidermal Langerhans Cells.

The presence of IgE-bearing epidermal Langerhans cells (LC) has been reported not only in patients with atopic eczema (AE) but also in patients with various inflammatory dermatoses unrelated to atopic diathesis. We have shown very recently that normal LC express the high-affinity receptor for IgE (FcεRI) which accounts for the binding of monomeric IgE on these cells. In the present study, we investigated the IgE-binding capacity of resident LC on cryosections from skin of normal individuals and from uninvolved and involved skin of patients with atopic eczema, psoriasis, lupus erythematosus and mycosis fungoides. When compared to LC from uninvolved or normal skin, an increased binding of IgE was observed in LC from lesional skin of all four diseases studied here. This binding could be blocked by anti-FcεRI mAb. Furthermore, increased IgE binding capacity of LC correlated to an increased expression of FcεRI on these cells. These results clearly demonstrate that the expression of FcεRI on LC is increased in inflammatory skin areas. Since this phenomenon is observed in several unrelated diseases, it suggests the presence in these conditions of a similar microenvironment which up-regulates the FcεRI expression on LC.

Gamma-Interferon Promotes the Release of IgE-Binding Factors (Soluble CD23) by Human Epidermal Langerhans Cells

In a previous study, we have demonstrated that human epidermal Langerhans cells (LC) are induced to express Fc epsilon R2/CD23 by stimulation with IL-4 and/or IFN-gamma. In this study, using LC-enriched and LC-depleted epidermal cell (EC) cultures, we have shown that stimulation with IL-4 and/or IFN-gamma not only led to Fc epsilon R2/CD23 expression on normal human LC but also to the release of significant amounts of IgE-BF (soluble CD23). Furthermore, stimulation with IL-4 was more effective in induction of Fc epsilon R2/CD23 on LC when compared to IFN-gamma, which, in contrast, strongly promoted the release of IgE-BF. These results indicate that Fc epsilon R2/CD23-positive LC represent a potential source of IgE-BF and that, as is observed in monocytes or U937 cells, IFN-gamma and IL-4 differently regulate the Fc epsilon R2/CD23 expression and release on LC.

T-Lymphocyte—Activating Properties of Epidermal Antigen-Presenting Cells from Normal and Psoriatic Skin: Evidence that Psoriatic Epidermal Antigen-Presenting Cells Resemble Cultured Normal Langerhans Cells

Fresh and cultured human Langerhans cells display disparate functional programs, based on their capacities to activate autologous and allogeneic T cells, and with respect to their susceptibility to inhibition by transforming growth factor-beta (TGF beta). We have compared the functional properties of epidermal antigen-presenting cells (APC) procured from uninvolved and involved skin of patients with psoriasis with fresh and cultured normal epidermal cells. Freshly obtained psoriatic epidermal APC resembled cultured normal epidermal cells in their superior capacity to activate syngeneic and allogeneic T cells; fresh normal epidermal cells failed to activate syngeneic T cells, and induced only modest proliferation among allogeneic T cells. The modest T-cell--activating properties of fresh, normal epidermal cells were not suppressed by TGF beta, whereas the T-cell--activating potential of psoriatic epidermal cells, cultured normal epidermal cells, and blood APC was inhibited approximately 50% by TGF beta. Thus, fresh psoriatic epidermal APC resemble cultured normal epidermal cells functionally. Because these properties are already evident in cells obtained from uninvolved psoriatic skin, the "cultured" functional phenotype of epidermal APC in this disease may precede the appearance of active psoriatic skin lesions. Surface marker analysis of normal and psoriatic epidermal cell suspensions revealed that virtually all of the bone marrow--derived cells in normal epidermal cell suspensions were conventional (CD1+) Langerhans cells, whereas CD1+ cells comprised only a minority of bone marrow--derived (CD45+) cells in psoriatic epidermis. It is speculated that some of the CD1-, CD45+ cells in psoriatic epidermis may be Langerhans cells that have lost their "fresh" phenotype. These data indicate that an abnormality in epidermal APC function exists in psoriatic skin--even before clinical lesions develop, and we speculate that the abnormal capacity of psoriatic epidermal APC to activate syngeneic T cells may be important in the expression of keratinocyte pathology. Because psoriatic epidermal APC functions were profoundly inhibited in vitro by treatment with cyclosporin A, the effectiveness of this drug in psoriasis may be due in part to its ability to inhibit epidermal antigen-presenting cell function in vivo.

Human Epidermal Langerhans Cells Express Integrins of the β1 Subfamily

The expression of VLA integrins on human epidermal Langerhans cells (LC) was investigated by indirect immunogold labeling on transmission electron microscopy, followed by a quantitative analysis. Labelings on suspensions enriched in freshly isolated LC were carried out with an antibody recognizing the beta 1 subunit, common to all members of the VLA family, and with antibodies specific for the six different alpha subunits, alpha 1 to alpha 6. Normal human epidermal LC were all beta 1 positive, of which 60% were highly positive. By labelings with different VLA-alpha-chain MoAb, there appeared two subpopulations of LC: one positive and one negative. On average 40% of LC bore small amounts of VLA-1 and VLA-3, 53% and 77% of LC expressed moderate amounts of VLA-2 and VLA-5, respectively, and VLA-4 and VLA-6 were expressed by 67% and 90% of LC, respectively. VLA proteins are mainly extracellular matrix protein receptors. VLA-6 (laminin receptor) and VLA-5 (fibronectin receptor) are expressed mainly by LC, and in this way could subserve LC to leave the epidermal compartment through the basement membrane, to migrate throughout the fibronectin network of the dermis before migrating via the afferent lymphatics to the regional lymph nodes, where they present antigen to T cells. VLA proteins such as VLA-4, VLA-3, or VLA-2, which are found involved in cell-cell contacts, could contribute to the promotion of T-cell activation by facilitating adherence between LC and T cells.

Antigen-Presenting Cells in Essential Fatty Acid—Deficient Murine Epidermis: Keratinocytes Bearing Class II (Ia) Antigens May Potentiate the Accessory Cell Function of Langerhans Cells

Essential fatty acid deficiency (EFAD) is a useful model for studying the role of (n-6) fatty acid metabolism in normal physiology. Because cutaneous manifestations are among the earliest signs of EFAD and because abnormalities in the distribution and function of tissue macrophages have been documented in EFAD rodents, we studied the distribution and function of Class II MHC (Ia) antigen-bearing cells in EFAD C57B1/6 mouse epidermis. Immunofluorescence studies revealed 1.9-9.6 (mean +/- SEM = 5.2 +/- 2.6) times more class II MHC (Ia) antigen-bearing epidermal cells in suspensions prepared from EFAD as compared to normal skin. Analysis of epidermal sheets demonstrated similar numbers of dendritic Ia+ and NLDC145+ cells in EFAD and normal epidermis, however. This discrepancy occurred because some keratinocytes in EFAD epidermal sheets expressed class II MHC (Ia) antigens, whereas keratinocytes in normal mouse epidermis did not. Two-color flow cytometry confirmed that all Ia+ cells in normal epidermis are Langerhans (Ia+ NLDC145+) cells, whereas Ia+ cells in EFAD epidermis are comprised of Langerhans cells and a subpopulation of keratinocytes (Ia+ NLDC145-). Similar levels of Ia antigens were expressed on EFAD and normal Langerhans cells. EFAD and normal epidermal cells were also compared in several in vitro assays of accessory cell function. Epidermal cells prepared from EFAD C57B1/6 mice present the protein antigen DNP-Ova to primed helper T cells more effectively than epidermal cells prepared from normal animals. EFAD epidermal cells are also more potent stimulators of T cells in primary and secondary allogeneic mixed lymphocyte-epidermal cell reactions than normal epidermal cells. The functional differences between EFAD and normal epidermal cells do not appear to result from increased cytokine release or decreased prostaglandin production by EFAD epidermal cells. In view of these findings and the observation that the antigen-presenting cell activity of EFAD epidermal cells correlates with the number of Ia+ keratinocytes in epidermal cell preparations, Ia+ keratinocytes (in the presence of Langerhans cells) may potentiate cutaneous immune responses in vitro and perhaps in vivo as well. These results also suggest that (n-6) fatty acids or metabolites of (n-6) fatty acids are involved in regulating the expression of class II MHC (Ia) antigens by keratinocytes in vivo.

Fc Receptors of Human Langerhans Cells

Receptors for the Fc fragment of immunoglobulins (Fc R) exhibit specificities for a wide variety of immunoglobulin classes and subclasses. In humans, at least three distinct classes of receptors for the Fc fragments of IgG (Fc gamma RI, II, III) and two classes of receptors for the Fc fragments of IgE (Fc epsilon RI, II) have been characterized. These classes were largely defined on the basis of their affinities for different immunoglobulin subclasses and their reactivities with monoclonal anti-receptor antibodies. Among these FcR, in healthy individuals, epidermal Langerhans cells (LC) express only the Fc gamma RII/CDw32. This FcR--a member of the immunoglobulin superfamily--is only present on about 50% of freshly isolated CD1a positive cells, as determined by rosette assays. It has a Mr of 40 kDa, is trypsin resistant, binds polymeric human IgG and murine IgG1-coated erythrocytes, and reacts with anti-CDw32 monoclonal antibodies (MoAb). LC internalize Fc gamma RII by receptor-mediated endocytosis. After 48 h of culture, human LC loose their Fc gamma RII, as revealed by flow cytometry. While the function(s) of the Fc gamma RII on human LC remain(s) unknown, this receptor may be primarily involved, like the Fc gamma RII present on mouse macrophages, in the clearance of extra-cellular immune complexes. In patients with atopic dermatitis having an elevated IgE serum level, beside an increased expression of the Fc gamma RII by LC located on lesional skin, IgE-bearing epidermal and dermal LC are present, again essentially on lesional skin. Double immunolabeling on cryosections reveals that on lesional skin only about 50% of the epidermal CD1a positive cells bear IgE. This capacity of LC to bind IgE molecules appears to be due to the presence of a specific Fc epsilon R. While the class of this Fc epsilon R still remains unclear, it appears to have some particularities: i) an associated expression with the CD1a antigen, ii) an affinity for IgG, and iii) a trypsin resistance. In vitro, human recombinant interleukin (IL)-4 and/or interferon (IFN)-gamma are able to induce the synthesis and expression of Fc epsilon RII/CD23 on a percentage of normal human epidermal LC. This Fc epsilon RII seems to be functional since it binds IgE molecules, this binding being prevented by preincubation with anti-CD23 MoAb.(ABSTRACT TRUNCATED AT 400 WORDS)

An ultraviolet B radiation protocol for complete depletion of human epidermal Langerhans cells.

We report an ultraviolet B (UVB) protocol that achieves essentially complete depletion of Langerhans cells (LC) from human skin, while leaving the skin clinically intact. Sixteen human volunteers of skin types II and III were exposed to 144 mJ/cm2 of UVB each day for 4 successive days, on a 2-cm-diameter circle of buttock skin. In each case the irradiated skin showed redness and mild edema but no vesiculation or ulceration. One hour after the last exposure a 4-mm punch biopsy was taken from the center of the irradiated site. The epidermal sheet from each sample was separated and exposed to CD-1 antibody (12 samples) or HLA-DR antibody (4 samples) and the density of LC was assessed by immunofluorescence light microscopy. In each case the epidermal LC population was severely depleted to less than 20 cells/mm2, from a baseline of approximately 565 cells/mm2, and in many cases no morphologically normal LC remained. This simple protocol thus provides intact human skin completely depleted of LC. Such skin will provide an appropriate model for the in vivo study of the immune function in human skin deprived of its epidermal antigen-presenting capacity.

Interferon Gamma Is a Marker for Histiocytosis X Cells in the Skin

In histiocytosis X (HX), which is regarded as a proliferative disease of Langerhans cells (LCs), the tumor cells share characteristic membrane antigens and ultrastructural features with normal LCs. To the present no markers have been described which distinguish HX cells from normal epidermal LCs. Here we report on the selective reactivity of HX cells with a monoclonal antibody against interferon gamma (IFNg). Our results show that HX cells share an epitope with human IFNg while normal LCs do not. It remains to be established whether the expression of IFNg is specific for HX cells or rather characterizes a certain activation state of LCs.

Absence of Langerhans Cells in Oral Hairy Leukoplakia, an AIDS-Associated Lesion

Oral hairy leukoplakia (HL) is a recently described manifestation of human immunodeficiency virus (HIV) infection in which Epstein-Barr virus (EBV) has been shown to replicate. To seek evidence for a local defect in mucosal immunity, we assessed the presence of epithelial Langerhans cells (LC) in these lesions and in autologous nonlesional mucosa. We used monoclonal antibodies against HLA-DR, HLA-DQ, and T6 antigens to identify LC in biopsy specimens of HL from 23 homosexual men. In all lesion specimens, LC either were not detected or were present only in greatly reduced numbers with at least 1 of the antibodies. In nonlesional oral mucosa from the same patients, LC were detected with all 3 antibodies in 11/12 specimens (92%) and were found in approximately normal numbers with at least 1 antibody. There was close correlation between the absence of LC and positive staining for EBV, human papillomavirus antigens, and candidal hyphae in the epithelium. We conclude that LC are absent or greatly reduced in the lesions of HL. Absence of normal LC function may be important in the pathogenesis of HL and may reflect an event in the pathogenesis of other features of the acquired immune deficiency syndrome.

Cutaneous infiltrates of histiocytosis X contain plasminogen activator-bearing epidermotropic dendritic cells different from Langerhans cells.

Plasminogen activators (PA) play an important role in cell migration and tissue degradation. Considering the strong epidermotropism of atypical mononuclear cells in histiocytosis X (HX) skin infiltrates leading to intraepidermal abscess formation, it was the purpose of this study to look for tissue-type PA (t-PA) and/or urokinase-type PA (u-PA) on HX cells. Four monoclonal antibodies against PA were used, employing the alkaline phosphatase anti-alkaline phosphatase (APAAP) technique on cryostat sections from four patients with HX. Twenty percent to 40% of infiltrating cells in the epidermis expressed the t-PA antigen. t-PA+ cells were present in the follicular centers of human tonsil, absent in normal epidermis and scanty in cutaneous infiltrates from mycosis fungoides and lupus erythematosus. Double labeling with anti-PA and T6 (CD1) or S100 protein revealed some of the HX cells to express both antigens (t-PA+ CD1+ or t-PA+ S100+). We conclude that cutaneous infiltrates of HX contain PA+ dendritic cells which are different from normal Langerhans cells and which may be responsible for the strong epidermal alterations in HX.

Langerhans cells in connective tissue diseases.

We have conducted a quantitative analysis of Langerhans cells (LC) in skin biopsies of 20 patients with various connective tissue diseases. Clinically normal skin of SLE patients as well as lesional skin of DLE showed consistently normal LC densities as assessed using ATPase staining, anti-DR and anti-OKT6. Examination of LC in clinically involved skin of patients with scleroderma revealed an absolute or relative decrease in ATPase and OKT6 expression, while staining with anti-DR gave inconclusive results. Clinically normal skin of the same individuals showed basically normal LC density. These findings suggest that the perturbation of the LC population is probably an expression of a secondary local phenomenon, and does not reflect a more widespread derangement of the accessory cells in the skin.

Ultrastructural observations in lichen nitidus.

Lichen nitidus (LN) and lichen planus (LP) are considered by some investigators to be two variants of the same disease, and by others to be two distinct dermatoses. In order to obtain further information about the relationship between LN and LP we examined the ultrastructure of lesions from two LN patients. In the central part of the lesion, the basement membrane was absent, or was interrupted by migrating phagocytes or lymphocytes. The basal cells and the lower cells of the stratum spinosum exhibited karyolysis and appeared to be compressed and often necrotic. In the upper dermis irregular cell debris full of clumps of tonofilaments and colloid-body-like structures was observed. A dense dermal infiltrate of macrophages, lymphocytes, fibrocytes, and Sezary-like cells was present. Signs of cooperation between lymphocytes and macrophages were also evident. The periphery of the lesion showed no pathological features except for enlargement of the intercellular spaces and the presence of mononuclear cells scattered through the epidermis. Several normal Langerhans cells were noticed. These ultrastructural findings were quite similar to those reported for LP.

Involvement of prostaglandins in the immune alterations caused by the exposure of mice to ultraviolet radiation.

Our study was designed to analyze the possible involvement of prostaglandins in the mechanisms responsible for the depressions in contact hypersensitivity (CH) responsiveness observed in UVR-exposed animals. Low-dose UVR-exposed animals were found to exhibit a depressed capacity to elicit CH responses after hapten application to irradiated (devoid of Langerhans cells) or UVR-protected (normal Langerhans cells) dorsal skin surfaces. Normal responsiveness was observed in low-dose UVR-exposed animals sensitized through unirradiated ventral skin surfaces. Indomethacin treatment of low-dose UVR-exposed animals (to inhibit prostaglandin synthesis in vivo) caused a retention in the capacity to respond normally to CH induction to haptens applied to the nonirradiated, but not to irradiated, dorsal skin surfaces. High-dose UVR-exposed animals, which normally exhibit a depression in responsiveness to hapten sensitization, retained a normal capacity to elicit CH responses if treated with the drug indomethacin. These findings implicate prostaglandins in the pathogenesis of the immunologic hyporesponsiveness, observed in low- and high-dose UVR-exposed animals. Our studies also determined that under all experimental conditions where animals were contact sensitized through nonirradiated skin sites, CH-effector cells could be found in the draining lymph nodes. No CH-effector cells were observed in the lymph nodes of mice that were contact sensitized directly through irradiated skin sites. It was also found that the spleens of both UVR-exposed and normal animals contained adoptively transferrable suppressor cells subsequent to hapten application. This demonstration of CH-effector and CH-suppressor cells in both normal and UVR-exposed animals did not directly relate to the potential of the donor animals to elicit a CH response.