Open AccessDirect Toll‐Like Receptor 8 signaling increases the functional avidity of human CD8+ T lymphocytes generated for adoptive T cell therapy strategies
Author(s) -
Chatillon JeanFrançois,
Hamieh Mohamad,
Bayeux Florence,
Abasq Claire,
Fauquembergue Emilie,
Drouet Aurélie,
Guisier Florian,
Latouche JeanBaptiste,
Musette Philippe
Publication year - 2015
Publication title -
immunity, inflammation and disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 18
ISSN - 2050-4527
DOI - 10.1002/iid3.43
Subject(s) - cytotoxic t cell , adoptive cell transfer , granzyme b , granzyme , immunology , cd8 , avidity , biology , antigen , perforin , immunotherapy , granzyme a , cancer research , t cell , in vitro , immune system , biochemistry
Adoptive 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.