1. ^*Department of Dermatology, Philipp University, Marburg, Germany
2. ^†The Jackson Laboratory, Bar Harbor, Maine, USA
3. ^‡Department of Tumor Progression and Immune Defence, German Cancer Research Center, Heidelberg, Germany
4. ^§Department of Biostatistics, German Cancer Research Center, Heidelberg, Germany
5. ^¶Department of Applied Genetics, University of Karlsruhe, Karlsruhe, Germany

Correspondence: Pia Freyschmidt-Paul, MD, Department of Dermatology, Philipp University, Deutschhausstrasse 9, 35033 Marburg, Germany. Email: freyschm@mailer.uni-marburg.de

¹Equal contributions.

Received 22 January 2005; Revised 30 April 2005; Accepted 16 May 2005.

Abstract

Alopecia areata (AA) is an autoimmune hair loss disease, that can be transferred between C3H/HeJ mice by skin grafting. We explored whether AA susceptibility is influenced by the availability of interleukin (IL)-2, a cytokine with leukocyte activating and regulatory properties. Mice heterozygous for a targeted deletion of IL-2 from the histocompatible C3.129P2(B6)-Il2^tm1Hor substrain, that produce reduced levels of IL-2, were examined for AA development after grafting skin from AA-affected C3H/HeJ mice. After grafting, nine of 19 (47%) heterozygous IL-2^+/-versus 16 of 18 (88%) IL-2^+/+ wild-type littermates developed AA. Although dense follicular leukocyte infiltrates were apparent in AA affected wild-type mice, AA-developing IL-2^+/- littermates had a reduced leukocyte infiltration, and AA-resistant IL-2^+/- mice had no inflammation. Lymph node cell analysis revealed a reduction in leukocyte activation markers in AA-developing IL-2^+/- mice. IL-2^+/- mice presented with low level expression of cytokines (IL-4, IL-10, interferon-, transforming growth factor-), upregulation of tumor necrosis factor receptors, and increased leukocyte apoptosis susceptibility independent of AA expression. In the skin, CD4⁺ cells and monocytes were reduced; activation markers were not upregulated and very few CD44v3⁺ or CD44v10⁺ leukocytes were recovered. Taken together, our data suggest that AA resistance of IL-2^+/- mice is because of the failure of activated leukocyte recruitment, thus pointing toward an involvement of IL-2 in AA pathogenesis.