TY - JOUR
T1 - IL-7 is superior to IL-2 for ex vivo expansion of tumourspecific CD4 + T cells
AU - Caserta, Stefano
AU - Alessi, Patrizia
AU - Basso, Veronica
AU - Mondino, Anna
PY - 2010/2
Y1 - 2010/2
N2 - It is well established that tumours hinder both natural and vaccine-induced tumourspecific CD4+ T-cell responses. Adoptive T-cell therapy has the potential to circumvent functional tolerance and enhance anti-tumour protective responses. While protocols suitable for the expansion of cytotoxic CD8+ T cells are currently available, data on tumour-specific CD4+ T cells remain scarce.We report here that CD4+ T cells sensitized to tumour-associated Ag in vivo, proliferate in vitro in response to IL-7 without the need for exogenous Ag stimulation and accumulate several folds while preserving a memory-like phenotype. Both cell proliferation and survival accounts for the outgrowth of tumoursensitized T cells among other memory and naive lymphocytes following exposure to IL-7. Also IL-2, previously used to expand anti-tumour CTL, promotes tumour-specific CD4+ T-cell accumulation. However, IL-7 is superior to IL-2 at preserving lymphocyte viability, in vitro and in vivo, maintaining those properties, that are required by helper CD4+ T cells to confer therapeutic efficacy upon transplantation in tumour-bearing hosts. Together our data support a unique role for IL-7 in retrieving memory-like CD4+ T cells suitable for adoptive T-cell therapy.
AB - It is well established that tumours hinder both natural and vaccine-induced tumourspecific CD4+ T-cell responses. Adoptive T-cell therapy has the potential to circumvent functional tolerance and enhance anti-tumour protective responses. While protocols suitable for the expansion of cytotoxic CD8+ T cells are currently available, data on tumour-specific CD4+ T cells remain scarce.We report here that CD4+ T cells sensitized to tumour-associated Ag in vivo, proliferate in vitro in response to IL-7 without the need for exogenous Ag stimulation and accumulate several folds while preserving a memory-like phenotype. Both cell proliferation and survival accounts for the outgrowth of tumoursensitized T cells among other memory and naive lymphocytes following exposure to IL-7. Also IL-2, previously used to expand anti-tumour CTL, promotes tumour-specific CD4+ T-cell accumulation. However, IL-7 is superior to IL-2 at preserving lymphocyte viability, in vitro and in vivo, maintaining those properties, that are required by helper CD4+ T cells to confer therapeutic efficacy upon transplantation in tumour-bearing hosts. Together our data support a unique role for IL-7 in retrieving memory-like CD4+ T cells suitable for adoptive T-cell therapy.
KW - Adoptive T-cell therapy
KW - Cytokines
KW - T helper cells
KW - Tumour immunology
UR - http://www.scopus.com/inward/record.url?scp=75149127319&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=75149127319&partnerID=8YFLogxK
U2 - 10.1002/eji.200939801
DO - 10.1002/eji.200939801
M3 - Article
C2 - 19950184
AN - SCOPUS:75149127319
VL - 40
SP - 470
EP - 479
JO - European Journal of Immunology
JF - European Journal of Immunology
SN - 0014-2980
IS - 2
ER -