Patients with or without a clonal mast cell disease undergoing venom immunotherapy differ in their CD8 T memory cell response

Hymenoptera venom immunotherapy (VIT) is usually effective in inducing long-term tolerance to the allergen. In patients with a clonal mast cell disease (CMD) and Hymenoptera venom-induced anaphylaxis, however, life-long VIT is recommended, as tolerance to the venom is often lost after VIT termination. We compared blood samples from patients with CMD and non-CMD with severe Hymenoptera venom-induced anaphylaxis before and more than 3 years after VIT to identify differences that might explain the lack of long-term tolerance in patients with CMD. Serum tryptase, IgE, IgG4, KIT D816V variation, as well as circulating T and B cell subsets, were analyzed. In addition, the cytokine response of wasp venom-stimulated PBMCs was measured. VIT-treated patients with CMD had higher numbers of CD8 effector memory T cells, while VIT-treated patients without CMD showed higher frequencies of CD8 central memory T cells compared to those in patients prior to VIT. The IL-6 response to wasp venom was lower in patients with CMD, regardless of anaphylaxis and therapy status. The generation of CD8 central memory T cells during VIT may be necessary for long-term tolerance to wasp venom after VIT.