Quatitation of Dendritic Cells in Normal and Abnormal Human Epidermis Using Monoclonal Antibodies Directed Against Ia and HTA Antigens

MacKie, Rona M.; Turbitt, Marlyn L.

doi:10.1111/1523-1747.ep12517998

Cited by 89 publications

(28 citation statements)

References 14 publications

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“…Again, although not statistically significant, the number was less compared with normal control sites. 33 The numbers of MHC class II ϩ cells remained more or less constant, suggesting that emigrating Langerhans cells (positive for CD1 and MHC class II) were replaced by immigrating MHC class II ϩ monocytes or macrophages. Eight hours after challenge more CD5 ϩ cells were seen in the epidermis than CD2 ϩ cells or CD4 ϩ and CD8 ϩ cells taken together.…”

Section: Discussionmentioning

confidence: 99%

“…In the uppermost portion of the dermis, vasodilatation, perivascular edema, and cellular infiltration were present, overall scored at 17.0 (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29). Subsequently, these changes increased and reached maximal intensity 24-48 hours after challenge (scores 31.5 and 33.0 [27][28][29][30][31][32][33][34][35][36], respectively). The epidermis showed pronounced acanthosis associated with many mitotic or vacuolated keratinocytes and moderately heavy spongiosis.…”

Section: Histopathologymentioning

confidence: 99%

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Morphologic and Immunohistochemical Features of Experimentally Induced Allergic Contact Dermatitis in Göttingen Minipigs

Vana

Meingassner

2000

Vet Pathol

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Abstract. Many preclinical studies in investigative dermatology are performed preferably in pigs because pig skin is more similar to human skin than is rodent skin. A frequently used model is allergic contact dermatitis (ACD); however, this T-cell-mediated skin condition so far is not well characterized in pigs. The present study is aimed at the evaluation of morphologic and immunohistochemical features of experimentally induced acute ACD in Göttingen minipigs using 2,4-dinitrofluorobenzene (DNFB) as a hapten. Eight minipigs were sensitized with 10% DNFB and challenged 2 weeks later at different sites with 1% DNFB. In addition to clinical examinations, cutaneous blood flow was quantified by laser Doppler velocimetry (Periflux PF3). These examinations were performed before challenge and 8, 24, 48, and 72 hours after challenge. Skin biopsies were taken at the same time points, fixed, sectioned, and stained with Giemsa for histologic evaluation, or with mouse anti-swine monoclonal antibodies (CD1, CD2, CD4, CD5, CD8, CD25, CD45, MHCII) and with one mouse anti-human monoclonal antibody (CD62E) cross-reacting with swine for immunohistochemical evaluation. Positively stained cells were counted per square millimeter of epidermis and dermis by using a video image analyzing system (Videoplan Kontron). Erythema and cutaneous blood flow peaked at 24 hours. The major epidermal changes most pronounced at 48 hours were acanthosis, spongiosis, intracellular edema, exocytosis, and abscesses mainly containing neutrophils and mononuclear cells (MNC). Perivascular infiltrates of MNC as well as neutrophils and eosinophils were the most significant dermal changes, with peak levels at 24-48 hours. In biopsies taken before challenge, CD1ϩ dendritic cells were found in similar numbers and locations as MHCII ϩ cells in the epidermis. In the epidermis the maximum CD1 ϩ cell decrease occurred at 24 hours whereas in the dermis the maximum increase in CD1 ϩ stained cells was seen at 72 hours. The dermal infiltrate (CD2 ϩ , CD5 ϩ , CD25 ϩ , and CD45 ϩ ) was most dense at 48 hours. Between 8 and 48 hours more CD4 ϩ were present than CD8 ϩ cells, whereas at 72 hours CD4 ϩ and CD8 ϩ cells were similar in numbers. These findings closely resemble changes in human ACD. Therefore, DNFB-induced ACD in Göttingen minipigs is considered to be an appropriate animal model to study immunopathologic mechanisms and pharmacologic intervention.Key words: Allergic contact dermatitis; 2,4-dinitrofluorobenzene; Göttingen minipig; histopathology; immunohistochemistry; skin inflammation; swine.Preclinical research in biomedical science uses laboratory animals to profile new compounds for possible uses as drugs. Therefore, laboratory animals serve either as models for the assessment of pharmacodynamic effects or, in advanced stages of drug development, for the identification of untoward effects (toxicities) of drug candidates. Therefore, the results obtained from animal pharmacology or animal toxicology studies should be reliably predictive for the situation in hum...

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Section: Discussionmentioning

confidence: 99%

Section: Histopathologymentioning

confidence: 99%

Morphologic and Immunohistochemical Features of Experimentally Induced Allergic Contact Dermatitis in Göttingen Minipigs

Vana

Meingassner

2000

Vet Pathol

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“…However, we were unable to demonstrate LC in a normal skin specimen from 1 subject, even in a repeated attempt with higher concentration of the antibody; yet LC were clearly demonstrated in all other specimens from the same patient. Monoclonal T6 antibodies consistently identify more LC than similar antibodies against la-like antigens (9,10), and both methods provide better tissue morphology than ATpase histochemistry. In normal human epidermis, subsets of LC have been identified as la + T6+ and la-/T6+, suggesting that expression of la-like antigens on LC may be analogous to la inducibility on macrophages (9).…”

Section: Discussusionmentioning

confidence: 90%

Expression of OKT6 antigen by Langerhans cells in patch test reactions

Christensen¹,

Daniels²,

Maibach³

1986

Contact Dermatitis

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Previous studies in humans and guinea pigs indicate that Langerhans cells (LC) participate in elicitation of allergic contact dermatitis. The number and morphology of LC was determined in acute and healed allergic patch test sites, control (petrolatum) sites and normal skin in nickel-sensitive individuals using OKT6 monoclonal antibody and avidin-biotin/peroxidase labeling. Compared to normal skin, the staining intensity and number of epidermal LC was significantly increased in allergic (p < 0.02) and petrolatum control (p < 0.02) sites, and in 6-to 8-week old allergic patch test sites (p < 0.006). The in situ changes in LC induced by petrolatum alone may be a result of the occlusive patch test, or may suggest that petrolatum is not as neutral as previously believed. The nickel-induced increase in LC may indicate changes in the LC present in the epithelium at the time of testing, or migration of additional LC into the epithelium, which can then remain in situ for weeks after the antigenic challenge. The specificity of the LC increase in allergic contact dermatitis is questioned on the basis of the increase noted with petrolatum. Key words: Langerhans cells -patch test reactions.Acceptedfor publication July 15, 1985 Langerhans cells (LC) have been implicated in the induction and elicitation of allergic contact dermatitis (1). Electron microscopic studies reveal apposition of lymphocytes and LC in the epidermis and dermis of allergic but not irritant patch test reactions. Signs of LC activation and LC cell damage (appearance of glycogen granules, rarefaction of cytoplasm and dilatation of perinuclear space) occur during elicitation of contact allergic dermatitis. Utilizing the L-dopa and catecholamine method to visualize LC, Sjoborg et al. (2) showed increased numbers of LC in guinea pig and human epidermis with allergic contact dermatitis. With the same method, Uno & Hanifin (3) found a high number of LC in chronic lesions of atopic dermatitis.The monoclonal anti-T6 antibody provides * Place where study was performed.a specific (4-6) and sensitive (7) probe for LC in the skin, and the avidin-biotin/peroxidase complex (ABC) labeling method has been shown to be more sensitive than the peroxidase-antiperoxidase method in demonstrating polypeptides (8). Consequently, we applied the T6 antibody and ABC labeling to study the occurrence and appearance of LC in human patch test reactions, control patch tests without antigen, and normal skin. We also studied LC in patch test sites up to 8 weeks after antigenic challenge. Material and MethodsSubjects 7 volunteers (5 female and 2 male, 29 to 71 years old) hypersensitive to nickel (proved by earlier patch testing) enrolled in this study after giving informed consent. 4 subjects, studied for short-term changes in allergic contact test

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“…In several cutaneous disorders such as lichen planus [27], cutaneous T-cell tymphoma [28], allergic contact dermatitis [15], and lupus erythematosus [1] keratinocytes have been shown to express HLA-DR antigens. The keratinocyte cell-surface HLA-DR expression is particularly seen overlying a dermal inflammatory infiltrate consisting largely of T lymphocytes.…”

Section: Discussionmentioning

confidence: 99%

In situ localization of interferons in psoriatic lesions

et al. 1989

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Summary. An indirect immunofluorescence technique, using murine monoclonal antibodies (MoAbs) against human IFN-~ and human IFN-? was used to study IFNs in cryostat sections from psoriatic skin lesions. The IFNs were more pronounced in sections from highly active psoriasis than in sections from stationary psoriasis. In highly active psoriatic lesions IFN-~ was localized to keratinocytes is stratum basale, to some epidermal dendritic cells, probably Langerhans cells, and to some mononuclear cells in dermis. IFN-~ was usually not detected in sections from stationary psoriasis. IFN-y was localized to stratum corneum, to keratinocytes around microabcesses and to mononnclear cells in the dermal cell infiltrates, predominantly in highly active psoriatic lesions. Both IFN-~ and IFNwere localized to some endothelial cells in the papillary dermis. The MoAbs did not stain sections from unaffected skin from patients with psoriasis or sections from healthy individuals. The findings indicate that the IFN system in the skin may be of significance in the pathophysiology of psoriasis. Key words: Psoriasis -InterferonsPreviously, we demonstrated interferon (IFN) in serum and suction blister fluid from patients with psoriasis using an infectivity inhibition micromethod [4]. Sera from patients with psoriasis had higher levels of IFN than sera from healthy individuals. Higher IFN levels were detected in suction blister fluid from psoriatic skin lesions than in serum and in suction blister fluid from unaffected skin, indicating IFN production in the skin lesions. Characterization experiments indicated the presence of IFN-7 and both acid labile and acid stable IFN-a in blister fluids and sera. Extended studies using an ELISA assay indicate inOffprint requests to ." J. K. Livden, MD (address see above) creased levels of IFN-? in sera from patients with active psoriasis compared with sera from healthy individuals, while sera from patients with stationary psoriasis have decreased levels of IFN-7 (unpublished data). Recently, Kapp et al. [11] found decreased IFN production by peripheral leukocytes from patients with psoriasis.IFN-7 is mainly produced by activated T lymphocytes, whereas IFN-~ is produced by several cell types after various viral and nonviral stimuli. Previously, we demonstrated retrovirus-like particles in suction blister fluids from psoriatic skin lesions [5]. The presence of IFN-a and retrovirus-like particles in blister fluids from psoriatic lesions indicated that virus may be of significance in the pathogenesis of psoriasis [23].Further information on IFN in psoriasis is of particular interest in relation to disease activity and cellular localization. Therefore, we examined sections of psoriatic and normal skin using an immunofluorescence technique with monoclonal antibodies to human IFN-~ and IFN-~.

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Quatitation of Dendritic Cells in Normal and Abnormal Human Epidermis Using Monoclonal Antibodies Directed Against Ia and HTA Antigens

Cited by 89 publications

References 14 publications

Morphologic and Immunohistochemical Features of Experimentally Induced Allergic Contact Dermatitis in Göttingen Minipigs

Morphologic and Immunohistochemical Features of Experimentally Induced Allergic Contact Dermatitis in Göttingen Minipigs

Expression of OKT6 antigen by Langerhans cells in patch test reactions

In situ localization of interferons in psoriatic lesions

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