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

Phenotypic and functional heterogeneity of porcine blood monocytes and its relation with maturation

Swine monocytes constitute a heterogeneous population of cells which can be divided into four subsets based on the expression of SWC3, CD14, CD163 and swine leucocyte antigen (SLA) DR markers. These subsets appear to represent different maturation stages in a pathway along which these cells up-regulate the expression of SLA DR and CD163 antigens and reduce that of CD14. Differences in the expression of adhesion and costimulatory molecules are also patent, with a progressive increase in the expression of CD11a, wCD11R1, CD29, CD49d, CD61, CD1a and CD80/86, and a concomitant decrease in that of wCD11R2. Besides, these subsets differ in their capacity for tumour necrosis factor-α (TNF-α) production in response to lipopolysaccharide + interferon-γ. The CD163(+) CD14(−) SLA DR(+) subset produces higher amounts of TNF-α than the CD163(−) CD14(+) SLA DR(−) subset, whereas CD163(+) CD14(+) SLA DR(+) and CD163(−) CD14(+) SLA DR(+) subsets show intermediate values. CD163(+) monocytes also display a higher ability to present soluble antigens to T cells than CD163(−) monocytes