L19.    The impact of a CD44 blockade on leukocyte migration in a skin-associated autoimmune disease treated by a contact allergen.
Pia Freyschmidt-Paul, Zöller Margot*, Pooja Gupta*, Mario Vitacolonna*, Susanne Hummel*; Department of Dermatology, Philipp University Marburg, *German Cancer Research Center, Heidelberg, Germany.

CD44 plays an important role in leukocyte migration. Anti-CD44 has been shown to mitigate delayed type hypersensitivity (DTH) reactions. In addition, induction of alopecia areata (AA) can be prevented by a CD44v10-specific antibody. On the other hand, AA can be cured a mild chronic eczema. Taking the therapeutic activity of anti-CD44 in AA as well as in DTH reactions, it became of interest to see whether both phenomena are based on the same or different mechanisms, which could give a hint, whether a combination of anti-CD44 treatment and induction of a mild chronic eczema would be contra-indicated or could be considered an improved therapeutics. To answer the question, the impact of anti-panCD44 and anti-CD44v10 was evaluated in repeatedly allergen (SADBE)-treated control and AA-affected mice. Anti-CD44 treatment had no impact on leukocyte activation in allergen-treated control and AA mice. Instead, anti-panCD44 and with equal efficacy anti-CD44v10 inhibited leukocyte migration in vivo and in vitro in untreated, AA and allergen treated control and AA mice. Anti-CD44-mediated inhibition of leukocyte migration was not accompanied by down-regulated expression of CD44 or of additional adhesion molecules, required for endothelial cell adhesion and extravasation. Instead, a blockade of CD44v10 interfered with leukocyte, most prominently with monocyte homing into the skin. Exclusively in AA affected mice, a panCD44-specific antibody also prevented T cell entry into the draining lymph node. In allergen-treated AA-affected mice there has been evidence that CD44v10 may additionally interfere with emigration of activated, chemokine receptor expressing T cells from the draining lymph node. We interpret the data in the sense that anti-CD44 prohibits extravasation of activated leukocytes despite the presence of adhesion molecules, chemokine receptors and chemoattractants. A blockade of CD44v10 selectively interferes with DTH and AA effector cells homing into the skin. A panCD44-specific antibody, though with lower efficacy, can also block leukocyte entry into the lymph node and/or egress of activated T cells from the draining node, which has mostly been seen in AA-affected mice. Thus, anti-CD44 treatment together with induction of a mild chronic eczema may well improve therapeutic efficacy in AA.