Efficient generation of survivin-specific cytotoxic T lymphocytes from healthy persons in vitro: quantitative and qualitative effects of CD4+ T cells.
For the adoptive immunotherapy and the study of cytotoxic T lymphocytes (CTLs) in human, efficient in vitro generation of CTLs is needed. However, it is still difficult to induce T cells specific for naïve antigens in vitro even though dendritic cells (DCs) as potent APCs are used. In this study, we investigated quantitative and qualitative effects of CD4+ T cells during in vitro stimulation of CD8+ T cells from healthy donors using DCs transduced with adenovirus vector expressing human survivin (Adv-survivin). CTLs were not efficiently induced in the absence of CD4+ T cells or in CD25+ depleted CD4+ T cells. When the ratio of CD4+:CD8+ T cells was quantitatively decreased from 2:1 to 1:2, proliferation of CTLs specific for survivin was gradually increased. Because DCs pulsed with HCMV pp65 protein could activate CD4+ T cells to secrete Th1 cytokines, the use of pp65 protein as an adjuvant induced higher numbers and frequencies of CTLs. Furthermore, Th1 conditioning of CD4+ T cells augmented this generation of CTLs. These results suggest that both quantitative and qualitative modulation of CD4+ T cells including the number and Th1 polarization may be required for the efficient induction of CTLs specific for tumor antigens in vitro.
Kim
Eun-Kyung
EK
Department of Microbiology, Catholic University of Korea, 505 Banpo-Dong, Seocho-Gu, Seoul, South Korea.
Cho
Hyun-Il
HI
Yoon
Sung Hee
SH
Park
Min-Ji
MJ
Sohn
Hyun-Jung
HJ
Kim
Hyung-Jin
HJ
Oh
Seong-Taek
ST
Kim
Tai-Gyu
TG
D000256:Adenoviridae / Q000235:genetics; D000276:Adjuvants, Immunologic; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000235:genetics / Q000502:physiology*; D003713:Dendritic Cells / Q000276:immunology*; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000276:immunology*; D009363:Neoplasm Proteins / Q000276:immunology*; D000077022:Survivin; D013601:T-Lymphocytes / Q000166:cytology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology
D000276:Adjuvants, Immunologic; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin; D014764:Viral Proteins