Blockade of thymic stromal lymphopoietin (TSLP) receptor inhibits TSLP-driven proliferation and signalling in lymphoblasts from a subset of B-precursor ALL patients.

Purpose: The cytokine thymic stromal lymphopoietin (TSLP) and its receptor TSLPR are involved in intercellular communication in the course of allergic inflammation and have recently been implicated in the development of various malignancies including B cell precursor acute lymphoblastic leukemia (BCP-ALL). We studied TSLPR expression, TSLP-induced signal transduction and its antibody-mediated inhibition in long-term cultures of primary cells derived from B-precursor ALL patients.

Methods: TSLPR expression was determined by flow cytometry and Western blot analysis, cell proliferation, signal transduction via the JAK/STAT pathway was analysed by Western blot detection of STAT tyrosine phosphorylation and by measuring TSLP-dependent activation of a STAT-specific reporter gene construct.

Expression analysis and specific blockade of the receptor for human thymic stromal lymphopoietin (TSLP) by novel antibodies to the human TSLPRα receptor chain.

Thymic stromal lymphopoietin (TSLP) is an interleukin-7 (IL-7)-like cytokine with a pivotal role in development and maintenance of atopic diseases such as allergic asthma and atopic dermatitis. Moreover, recent studies show an involvement of TSLP in the progression of various cancers. TSLP signaling is mediated by the TSLP receptor (TSLPR), a heterodimeric type I cytokine receptor.

Reduced suppressive effect of CD4+CD25high regulatory T cells on the T cell immune response against myelin oligodendrocyte glycoprotein in patients with multiple sclerosis.

Immunoregulatory T cells of (CD4+)CD25+ phenotype suppress T cell function and protect rodents from organ-specific autoimmune disease. The human counterpart of this subset of T cells expresses high levels of CD25 and its role in human autoimmune disorders is currently under intense investigation. In multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system (CNS), the activation of circulating self-reactive T cells with specificity for myelin components is considered to be an important disease initiating event.