Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Sunder-Plassmann, R; Breiteneder, H; Zimmermann, K; Strunk, D; Majdic, O; Knapp, W; Holter, W.
Single human T cells stimulated in the absence of feeder cells transcribe interleukin-2 and undergo long-term clonal growth in response to defined monoclonal antibodies and cytokine stimulation.
Blood. 1996; 87(12):5179-5184
Doi: 10.1182/blood.V87.12.5179.bloodjournal87125179
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- Co-Autor*innen der Med Uni Graz
- Strunk Dirk
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- Abstract:
- The two-signal model of T-cell activation postulates that T lymphocytes require at least two distinct signals for activation. This model has been established with bulk cultures of T cells in which T-cell-T-cell interaction can occur, possibly delivering further unrecognized costimulatory signals. The signal requirements of single T cells for the induction of clonal cell growth or the transcription of cytokines would best be studied in a cell cloning system in the absence of feeder cells; however, such an experimental system has not been reported so far. In this study, we report the long-term cloning of human resting peripheral blood CD4+CD45RO- T cells under feeder cell-free conditions in response to CD3 and CD28 stimulation in the presence of exogenous interleukin-2 (IL-2). Cloning efficiency ranged from 40% to 60% depending on the presence of additional cytokines IL-1 and IL-6. Single-call polymerase chain reaction showed that transcription of IL-2 occurred in cells stimulated through CD3 plus CD28 alone. T cells grown in response to CD3 plus CD28 plus IL-2 stimulation produced both IL-4 and interferon-gamma (IFN-gamma) on restimulation (Th0 cells) and could be functionally differentiated into Th1- or Th2-type cells by the addition of IFN-gamma or IL-4, respectively, during cell cloning. These data show on the single-cell level a two-signal model of T- cell activation for the transcription of IL-2. In addition, these experiments show that IFN-gamma and IL-4 exert their T-cell-differentiating effects directly on the T cell without any further need for antigen-presenting cells. Together, our experiments show the feasability of a defined long-term clonal cell culture system to study the growth and differentiation of human T lymphocytes.
- Find related publications in this database (using NLM MeSH Indexing)
- Antibodies, Monoclonal - immunology Antibodies, Monoclonal - pharmacology
- Antigens, CD28 - immunology
- Base Sequence -
- CD4-Positive T-Lymphocytes - drug effects CD4-Positive T-Lymphocytes - immunology
- Cell Differentiation - drug effects
- Cell Division - drug effects
- Cells, Cultured -
- Clone Cells -
- Cytokines - immunology Cytokines - pharmacology
- Gene Expression Regulation - drug effects
- Gene Rearrangement, beta-Chain T-Cell Antigen Receptor -
- Humans -
- Interferon-gamma - biosynthesis Interferon-gamma - pharmacology
- Interleukin-1 - pharmacology
- Interleukin-2 - biosynthesis Interleukin-2 - genetics Interleukin-2 - pharmacology
- Interleukin-4 - biosynthesis Interleukin-4 - pharmacology
- Interleukin-6 - pharmacology
- Lymphocyte Activation - drug effects
- Molecular Sequence Data -
- Polymerase Chain Reaction -
- Receptor-CD3 Complex, Antigen, T-Cell - immunology
- Th1 Cells - cytology
- Th2 Cells - cytology