Chronic delayed-type hypersensitivity reaction as a means to treat alopecia areata.
The acute phase of alopecia areata (AA) is characterized by an increase in CD44v3+ and CD44v10+ skin-infiltrating leucocytes (SkIL). Induction of a contact eczema, one of the therapeutic options in AA, can be mitigated strongly by a blockade of CD44v10. The observation that induction of a delayed type hypersensitivity (DTH) reaction abrogates an autoimmune reaction, where both responses apparently use similar effector mechanisms, is surprising and prompted us to search for the underlying mechanisms. AA-affected C3H/HeJ mice were treated with the contact sensitizer SADBE (squaric acid dibutylester) and leucocyte subpopulations and their activation state was evaluated in SkIL and draining lymph nodes. AA-affected mice exhibited an increased number of SkIL with a predominance of T lymphocytes. After treatment with the contact sensitizer SADBE recovery of SkIL was reduced and monocytes predominated. However, a significantly increased number of leucocytes was recovered from draining lymph nodes. Draining lymph node cells from untreated and treated AA mice exhibited all signs of recent activation with high-level expression of co-stimulatory and accessory molecules and an increased percentage of CD44v3+ and CD44v10+ leucocytes. In contrast, SkIL of SADBE-treated AA mice contained relatively few activated T cells and reduced numbers of CD44v3+ and CD44v10+ cells. Thus, the activation state and the distribution of leucocyte subsets in SADBE-treated AA mice are consistent with a blockade of leucocyte extravasation. Accordingly, the therapeutic effect of long-term SADBE treatment may rely on impaired leucocyte traffic.
Zöller
M
M
Department of Tumor Progression and Tumor Defense, German Cancer Research Center, Heidelberg, Germany. m.zoeller@dkfz.de
Freyschmidt-Paul
P
P
Vitacolonna
M
M
McElwee
K J
KJ
Hummel
S
S
Hoffmann
R
R
D000485:Allergens / Q000627:therapeutic use; D000506:Alopecia Areata / Q000276:immunology / Q000628:therapy*; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000628:therapy*; D002478:Cells, Cultured; D003503:Cyclobutanes / Q000627:therapeutic use; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D016130:Immunophenotyping; D007167:Immunotherapy / Q000379:methods*; D007962:Leukocytes / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D012867:Skin / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology
D000485:Allergens; D003503:Cyclobutanes; C020637:squaric acid dibutyl ester