P7.73 APOPTOSIS RESISTANCE IN PERIPHERAL BLOOD LYMPHOCYTES OF ALOPECIA AREATA PATIENTS

Kevin J. McElwee, Pia Freyschmidt-Paul, Margot Zöller* and Rolf Hoffmann

Department of Dermatology, Philipp University Marburg, Marburg, Germany and *Department of Tumor Progression and Tumor Defense, German Cancer Research Center, Heidelberg

Objectives: We recently noted in a mouse model of alopecia areata (AA) that CD4⁺CD25⁺ regulatory T cells (T_reg) are absent from draining lymph nodes and that expression of CD44v7 is transiently upregulated. Both features might explain autoreactive T cell persistence. Here we explored whether similar changes are seen in AA patients’ peripheral blood mononuclear cells (PBMC).

Results: As compared to healthy donors, PBMC from patients with progressive AA, as opposed to stable or regressive disease states, contained an increased percentage of CD4⁺CD25⁺ cells. The majority of these cells were not CD4⁺CD25⁺CD152⁺ T_reg, but rather they exhibited a freshly activated phenotype with expression of CD154 and weak inhibition of T cell proliferation. There was no clear evidence in the current study for a reduction in T_reg as a possible means to support sustained T cell activation. However, progressive AA patients’ PBMC did display increased resistance towards apoptosis. Apoptosis resistance was accompanied by a decrease in CD95L⁺ cells and an increase in CD44v7⁺ cells. Notably, the expanded population of CD4⁺CD25⁺CD154⁺ T cells in progressive AA patients’ PBMC was apoptosis resistant and expressed CD44v7.

Conclusions: Thus, survival of activated T cells in progressive AA patients’ PBMC is apparently sustained by downregulation of CD95L and upregulation of CD44v7, which is known to be associated with anti-apoptotic gene expression. It remains to be explored whether activated T cell expansion and survival in AA patients may be further supported by a reduction in T_reg, which could have been hidden by the prevalence of activated T cells.