Apoptosis resistance in peripheral blood lymphocytes of alopecia areata patients.
Alopecia areata (AA) is a putative, cell-mediated autoimmune disease of anagen stage hair follicles. Inter- and intra-follicular lymphocytic infiltrates are associated with alopecia that may progress from an initially patchy presentation to extensive, even universal, hair loss. We previously noted in a mouse model of AA that regulatory T cells (Treg) 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). There was no clear evidence for a reduction in Treg as a possible means to support sustained T cell activation. However, progressive AA patients' PBMC displayed increased resistance towards apoptosis, which was accompanied by a decrease in CD95L+ and an increase in CD44v7+ cells. Notably, an expanded population of CD4+CD25+CD154+ T cells in progressive AA patients' PBMC was apoptosis resistant and expressed CD44v7. 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.
Zöller
Margot
M
Department of Tumor Progression and Tumor Defense, German Cancer Research Center, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany. m.zoeller@dkfz.de
McElwee
Kevin J
KJ
Vitacolonna
Mario
M
Hoffmann
Rolf
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D000506:Alopecia Areata / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D017209:Apoptosis; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology; D015704:CD4 Antigens / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D002648:Child; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology*
D015704:CD4 Antigens; D015375:Receptors, Interleukin-2; D016753:Interleukin-10; D007371:Interferon-gamma