TY - JOUR
T1 - Autologous dendritic cells derived from CD34+ progenitors and from monocytes are not functionally equivalent antigen-presenting cells in the induction of Melan-A/Mart-127-35-specific CTLs from peripheral blood lymphocytes of melanoma patients with low frequency of CTL precursors
AU - Mortarini, Roberta
AU - Anichini, Andrea
AU - Di Nicola, Massimo
AU - Siena, Salvatore
AU - Bregni, Marco
AU - Belli, Filiberto
AU - Molla, Alessandra
AU - Gianni, Alessandro M.
AU - Parmiani, Giorgio
PY - 1997/12/15
Y1 - 1997/12/15
N2 - Peptide presentation by autologous dendritic cells (DCs) is a new tool to activate tumor antigen-specific T cells in melanoma patients. However, it is not known whether autologous DCs, differentiated by two of the most efficient protocols (from CD34+ progenitors or from monocytes), are equally effective as professional antigen-presenting cells (APCs) when the patients have a low frequency of peptide-specific precursors. To this end, a limiting dilution assay was applied to evaluate the frequency of antigen-specific CTL precursors (CTLps) in peripheral blood of HLA-A*0201+ melanoma patients. Then, from two melanoma patients showing low frequency of CTLps to melanoma antigen-A/melanoma antigen recognized by T cell (Melan-A/Mart-1)27-35 peptide, autologous DCs were differentiated from granulocyte colony- stimulating factor-mobilized CD34+ progenitors or from monocytes. CD34+- and monocyte-derived DCs were characterized by a similar proportion of CD1a+ cells expressing HLA class II antigens and CD54, CD80, and CD86 molecules. Both types of DC presented Melan-A/Mart-127-35 and tyrosinase369- 377 peptides to melanoma-specific CTL clones and were equally effective as peptide-pulsed APCs in the activation of influenza A matrix58-66- specific CTLs from high-frequency precursors (1294/106 and 1789/106 lymphocytes in the two patients). However, efficient activation of Melan- A/Mart-127-35-specific CTLs from low-frequency precursors (158/106 and 77/106 lymphocytes) of the two patients was markedly dependent on the use of peptide-loaded CD34+-derived DCs. These results suggest that CD34+and monocyte-derived DCs are not functionally equivalent APCs for the activation of low-frequency peptide-specific CTLps.
AB - Peptide presentation by autologous dendritic cells (DCs) is a new tool to activate tumor antigen-specific T cells in melanoma patients. However, it is not known whether autologous DCs, differentiated by two of the most efficient protocols (from CD34+ progenitors or from monocytes), are equally effective as professional antigen-presenting cells (APCs) when the patients have a low frequency of peptide-specific precursors. To this end, a limiting dilution assay was applied to evaluate the frequency of antigen-specific CTL precursors (CTLps) in peripheral blood of HLA-A*0201+ melanoma patients. Then, from two melanoma patients showing low frequency of CTLps to melanoma antigen-A/melanoma antigen recognized by T cell (Melan-A/Mart-1)27-35 peptide, autologous DCs were differentiated from granulocyte colony- stimulating factor-mobilized CD34+ progenitors or from monocytes. CD34+- and monocyte-derived DCs were characterized by a similar proportion of CD1a+ cells expressing HLA class II antigens and CD54, CD80, and CD86 molecules. Both types of DC presented Melan-A/Mart-127-35 and tyrosinase369- 377 peptides to melanoma-specific CTL clones and were equally effective as peptide-pulsed APCs in the activation of influenza A matrix58-66- specific CTLs from high-frequency precursors (1294/106 and 1789/106 lymphocytes in the two patients). However, efficient activation of Melan- A/Mart-127-35-specific CTLs from low-frequency precursors (158/106 and 77/106 lymphocytes) of the two patients was markedly dependent on the use of peptide-loaded CD34+-derived DCs. These results suggest that CD34+and monocyte-derived DCs are not functionally equivalent APCs for the activation of low-frequency peptide-specific CTLps.
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M3 - Article
C2 - 9407964
AN - SCOPUS:0031440468
VL - 57
SP - 5534
EP - 5541
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0008-5472
IS - 24
ER -