T-lymphocytes in atopic dermatitis

Van der Heijden, F.L., Wierenga, E.A., Bos, J.D. and Kapsenberg, M.L. (1991). High frequency of IL-4 producing CD4 allergen-specific T lymphocytes in atopic dermatitis leisonal skin. J. Invest. Dermatol. 97, 389-394. 

Vestergaard C, Deleuran M, Gesser B, Gronhoj Larsen C. Expression of the T-helper 2-specific chemokine receptor CCR4 on CCRIO-positive lymphocytes in atopic dermatitis skin but not in psoriasis skin. Br J Dermatol 2003 149 457-463. 

Microorganism Activate T Lymphocytes and Bystander Cells in the Skin in Atopic Dermatitis An important strategy by which S. aureus exacerbates atopic dermatitis is by secreting exotoxins. Some of them function as superantigens, which stimulate activation of T cells and major histocompatibility (MHC) class II + APC or keratinocytes, which express MHC class II upon activation. Many effects on T lymphocytes and other cells are elicited by superantigens (table 1). 

Akdis M, Simon H-U, Weigl L, Kreyden 0, Blaser K, Akdis CA Skin homing (cutaneous lymphocyte-associated antigen-positive) CD8+ T cells respond to superantigen and contribute to eosinophilia and IgE production in atopic dermatitis. J Immunol 1999 163 466-475. 

Pharmacology Tacrolimus is a macrolide immunosuppressant produced by Streptomyces tsukubaensis. The mechanism of action of tacrolimus in atopic dermatitis is not known. It has been demonstrated that tacrolimus inhibits T-lymphocyte activation by first binding to an intracellular protein, FKBP-12. Pharmacokinetics ... 

Chan S-C, Brown MA, Willcox TM, Li SH, Stevens SR, Tara D, Hanifin JM Abnormal IL-4 gene expression by atopic dermatitis T lymphocytes is reflected in altered nuclear protein interactions with IL-4 transcriptional regulatory element. J Invest Dermatol 1996 106 1131-1136. 

A murine model of food-induced atopic dermatitis confirmed the important role of specific T cells in eczema here, C3H/HeJ mice were orally sensitized to cow s milk or peanut and thereafter exposed to the allergen. An eczematous eruption developed in approximately one third of mice after low-grade exposure to milk or peanut proteins. Histological examination of lesional skin revealed spongiosis and a cellular infiltrate mainly consisting of CD4-I- lymphocytes. 

The role of both T and B lymphocytes in a variety of disease states beyond transplantation has become increasingly important in the past decade. This is especially true of those diseases frequently referred to as autoimmune in their etiology, such as rheumatoid arthritis, nephrotic syndrome, systemic lupus erythematosus, inflammatory bowel disease, and so on. In addition, several other major diseases are also known to have a component of T- or B-cell-mediated pathogenesis, for example, atopic dermatitis, psoriasis, and asthma. Until very recently, the mainstay of therapy for these diseases was the corticosteroids, which were often less than satisfactory in efficacy and often associated with undesirable side effects, especially in growing children and the elderly. Thus, the search for new agents with different mechanisms of action and which did not have the same adverse event profile as conventional corticosteroids led to the subsequent evaluation of drugs such as tacrolimus and sirolimus to treat several of these diseases. 

C23H26O6, Mr 422.46, prismatic cryst., mp. 156 C. p-Terphenyl derivative from cultures of Aspergillus candidus. T. in vitro inhibits the formation of immunoglobulin E in human lymphocytes (IC50 0.18 nM). It is investigated as lead structure for the synthesis of therapeutics against asthma, atopic dermatitis and other allergic diseases. 

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