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Minimal costimulatory requirements for T cell priming and TH1 differentiation: activation of naive human T lymphocytes by tumor cells armed with bifunctional antibody constructs.
- Source :
-
Cancer immunity [Cancer Immun] 2001 Nov 12; Vol. 1, pp. 10. Date of Electronic Publication: 2001 Nov 12. - Publication Year :
- 2001
-
Abstract
- Direct priming of naive human CD8+ and CD4+ T cells by tumor cells devoid of any intrinsic antigen presentation properties, but passively armed with recombinant proteins mediating primary and costimulatory T cell signals, was investigated. Bifunctional antibody constructs were used to specifically target costimulatory molecules such as B7-1, B7-2 and LFA-3 to the epithelial cell adhesion molecule (EpCAM), a surface antigen successfully used as target for antibody therapy of minimal residual colorectal cancer. T cell priming was monitored by flow cytometric analysis of CD45 isoform expression and confirmed by measuring typical effector functions of primed T cells known to be absent from naive T lymphocytes. Accordingly, CD8+ T cells were tested for cytotoxic activity and secretion of TNF-alpha, while secretion of IFN-gamma, IL-5 and IL-4 was determined for CD4+ T cells. B7, known to be required for the initial activation of naive T cells, also proved to be sufficient for T cell priming when present as the only costimulatory molecule together with an appropriate primary signal. The requirement of dendritic and other antigen presenting cells (APCs) for T cell priming through non-APCs such as tumor cells could be ruled out. Under minimal priming conditions, naive CD4+ T cells were found to exclusively enter the TH1 developmental pathway, while several factors thought to favor TH2 polarization, like weak primary signals and B7-2 versus B7-1 costimulation, could be excluded as dominant TH2 promoters.
- Subjects :
- Animals
Antibodies, Bispecific chemistry
Antibodies, Bispecific genetics
Antigen Presentation
Antigens, CD genetics
B7-1 Antigen genetics
B7-2 Antigen
CD4-Positive T-Lymphocytes immunology
CD58 Antigens genetics
CD8-Positive T-Lymphocytes immunology
CHO Cells
Cell Differentiation
Cells, Cultured
Cricetinae
Cytokines biosynthesis
Epithelial Cell Adhesion Molecule
Humans
Leukocyte Common Antigens metabolism
Membrane Glycoproteins genetics
Neoplasms immunology
Recombinant Proteins chemistry
Recombinant Proteins immunology
Th2 Cells immunology
Antibodies, Bispecific immunology
Antigens, Neoplasm immunology
Cell Adhesion Molecules immunology
Lymphocyte Activation
T-Lymphocytes immunology
Th1 Cells immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1424-9634
- Volume :
- 1
- Database :
- MEDLINE
- Journal :
- Cancer immunity
- Publication Type :
- Academic Journal
- Accession number :
- 12747771