Direct Toll-Like Receptor 8 signaling increases the functional avidity of human CD8+ T lymphocytes generated for adoptive T cell therapy strategies

International audienceAdoptive transfer of in vitro activated and expanded antigen-specific cytotoxic T lymphocytes (CTLs) is a promising therapeutic strategy for infectious diseases and cancers. Obtaining in vitro a sufficient amount of highly specific cytotoxic cells and capable of retaining cytotoxic activity in vivo remains problematic. We studied the role of Toll-Like Receptor-8 (TLR8) engagement on peripheral CTLs activated with melanoma antigen MART-1-expressing artificial antigen-presenting cells (AAPCs). After a 3-week co-culture, 3–27% of specific CTLs were consistently obtained. CTLs expressed TLR8 in the intracellular compartment and at the cell surface. Specific CTLs activated with a TLR8 agonist (CL075) 24 h before the end of the culture displayed neither any change in their production levels of molecules involved in cytotoxicity (IFN-γ, Granzyme B, and TNF-α) nor major significant change in their cell surface phenotype. However, these TLR8-stimulated lymphocytes displayed increased cytotoxic activity against specific peptide-pulsed target cells related to an increase in specific anti-melanoma CTL functional avidity. TLR8 engagement on CTLs could, therefore, be useful in different immunotherapy strategies

Proteomic analysis of the autoantibody response following immunization with a single autoantigen

International audienceIn most autoimmune diseases, the autoantibody response is directed against several antigens of the target organ whose identification is crucial for understanding the physiopathological process. Thus, technologies allowing a characterization of the whole autoantibody pattern of both human and experimental autoimmune diseases are required. Here we have used immunoproteomic analysis of human epidermal extracts to characterize the diversity of the anti-desmosome antibody response induced in normal mice immunized with desmoglein 1, the major autoantigen of pemphigus foliaceus, an autoimmune blistering skin disease. In particular, this analysis enables us to characterize the binding properties of anti-desmosome mAbs derived from these mice and to show that the autoantibody response induced upon immunization with a single autoantigen targets different epidermal autoantigens with a pattern similar to that observed in certain variety of human pemphigus

Outcome after failure of allogeneic hematopoietic stem cell transplantation in children with acute leukemia: a study by the société Francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC)

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