Transfer of CD8+ Cells Induces Localized Hair Loss Whereas CD4+/CD25− Cells Promote Systemic Alopecia Areata and CD4+/CD25+ Cells Blockade Disease Onset in the C3H/HeJ Mouse Model

Abstract

Alopecia areata (AA) is a suspected hair follicle specific autoimmune disease. The potential for cell transfer of AA using the C3H/HeJ mouse model was examined. Cells isolated from lymph nodes and spleens of AA-affected mice using magnetic bead conjugated monoclonal antibodies were subcutaneously injected into normal C3H/HeJ recipients. Within 5 wk, all CD8(+) cell-injected mice exhibited localized hair loss exclusively at the site of injection that persisted until necropsy. In contrast, some CD4(+) and CD4(+)/CD25(-) cell-injected mice developed extensive, systemic AA, and a combination of CD8(+) and CD4(+)/CD25(-) cells injected yielded the highest frequency of systemic AA induction. CD4(+)/CD25(+) cells were less able to transfer the disease phenotype, partially blockaded systemic AA induction by CD4(+)/CD25(-) cells, and prevented CD8(+) cell-induced, injection site-localized hair loss. CD11c(+) and CD19(+) cells failed to promote significant phenotype changes. Increases in co-stimulatory ligands CD40 and CD80, plus increased leukocyte apoptosis resistance with reduced CD95, CD95L, and CD120b expression, were associated with successful alopecia induction. The results suggest that CD8(+) cells may be the primary instigators of the hair loss phenotype. However, systemic disease expression fate is, apparently determined by CD4(+)/CD25(-) cells, while CD4(+)/CD25(+) lymphocytes may play a predominantly regulatory role.

Diagnostic Exercise: Severe Bilaterally Symmetrical Alopecia in a Horse

“…10 In the previously reported equine AA cases 3,5 and in the present case, CD3 þ T cells were demonstrated by immunohistochemistry. Further investigation to identify CD4 þ and CD8 þ subsets was not successful because of the lack of specific antibodies to the equine cluster of differentiation (CD) transmembrane proteins.…”

“…Alopecia areata is an uncommon immune-mediated hair loss that has been reported in various species including the humans, nonhuman primates, 2 dogs, 8 cats, 8 cattle, 14 chickens, 16 laboratory rodents, 10 and horses. 3,5,11,15 Clinically, AA is characterized by sudden or insidious, well-circumscribed, nonscarring, and visually noninflammatory alopecia.…”

In vivo CD44‐CD49d complex formation in autoimmune disease has consequences on T cell activation and apoptosis resistance

“…Here, we report that the CD44-CD49d association in a non-life threatening autoimmune disease [30,31] has, in addition, a strong bearing on T cell proliferation and survival. This effect is due to CD44 and CD49d mutually gaining access to the partner-associated linker and signal transducing molecules.…”

“…As a model, we choose alopecia areata (AA), an autoimmune disease affecting anagen stage hair follicles resulting in hair loss [30,31]. The human disease is closely mimicked by C3H/HeJ mice that develop AA spontaneously, or after the transfer of full thickness skin grafts [32].…”

Papel das células T reguladoras no desenvolvimento de dermatoses

“…76 Candidiasis During the experimental infection of mice with Candida albicans, the reduction in CD4+CD25+ high Treg cells induces a better control of infection, but it is associated with an increase of the intestinal inflammatory lesion. 77 PTherefore, the reduction of natural Treg cells leads to a better primary control of infections by C. albicans.…”