Infiltrating cells, related cytokines and chemokine receptors in lesional skin of patients with dermatomyositis.

Abstract

BACKGROUND:

There have been only two reports on immunophenotypic characterization in the cutaneous lesions of dermatomyositis (DM) that emphasize the importance of the infiltrating CD4+ T lymphocytes.

OBJECTIVES:

To characterize the immunophenotype of the cells that infiltrate the lesional skin of DM and to evaluate the possible T-helper (Th) polarization Th1/Th2 through detection of specific cytokines, chemokine receptors and markers of cellular activation.

METHODS:

Skin biopsy specimens derived from pathognomonic lesions (Gottron's papules and Gottron's sign) of eight patients with DM were immunostained with a large panel of monoclonal antibodies to CD3, CD4, CD8, myeloperoxidase (MPO), eosinophil cationic protein, tryptase, CD40, CD40 ligand (CD40L), HLA-DR, interleukin (IL)-2, IL-4, IL-5, IL-13, interferon-gamma, tumour necrosis factor-alpha, receptor 3 for CXC chemokines (CXCR3) and receptor 3 for CC chemokines, using the alkaline phosphatase-antialkaline phosphatase method. Control specimens were obtained from five healthy subjects and from six patients with discoid lupus erythematosus.

RESULTS:

Activated CD4+ Th lymphocytes (HLA-DR+ CD40L+) were the principal infiltrating cells in the lesional skin of DM; the CD4/CD8 ratio was approximately 2.5. A mixed Th1/Th2 profile and higher Th1 cytokine production together with significant staining for CXCR3 were detected. Neutrophil granulocytes were the second most abundant population; eosinophil granulocytes were very poorly represented.

CONCLUSIONS:

Activated CD4+ T cells presumably mediate the main pathogenetic mechanisms in pathognomonic skin lesions. The interaction between CD40 and CD40L could be an important mechanism of cellular activation in cutaneous immune-mediated inflammation by induction of secretion of proinflammatory cytokines and chemokines. Neither Th1 nor Th2 clear polarization was found, although there was a slight Th1 prevalence. There was a significant quantity of MPO+ cells (neutrophil granulocytes) in the inflamed tissue, and they might have a role in sustaining the chronic inflammation.

• Authors: M Caproni, D Torchia, C Cardinali, W Volpi, E Del Bianco, A D'Agata, P Fabbri
• Journal: The British journal of dermatology (Br J Dermatol) Vol. 151 Issue 4 Pg. 784-91 (Oct 2004) ISSN: 0007-0963 [Print] England
• PMID: 15491417 (Publication Type: Journal Article)

Chemical References

• Cytokines
• Receptors, Chemokine

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Chemotaxis, Leukocyte (immunology)
• Child
• Cytokines (metabolism)
• Dermatomyositis (immunology)
• Female
• Humans
• Immunoenzyme Techniques
• Immunophenotyping
• Lymphocyte Activation
• Middle Aged
• Receptors, Chemokine (metabolism)
• Skin (immunology)
• T-Lymphocyte Subsets (immunology)