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.

Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.

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 Jun 15;87(12):5179-84. Unique Identifier : AIDSLINE MED/96247520
Sunder-Plassmann R; Breiteneder H; Zimmermann K; Strunk D; Majdic O; Knapp W; Holter W; Institute of Immunology, University of Vienna, Austria.

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.

Keywords: Antibodies, Monoclonal/IMMUNOLOGY/*PHARMACOLOGY Antigens, CD28/IMMUNOLOGY Base Sequence Cell Differentiation/DRUG EFFECTS Cell Division/DRUG EFFECTS Cells, Cultured Clone Cells Cytokines/IMMUNOLOGY/*PHARMACOLOGY CD4-Positive T-Lymphocytes/DRUG EFFECTS/*IMMUNOLOGY Gene Expression Regulation/DRUG EFFECTS Gene Rearrangement, beta-Chain T-Cell Antigen Receptor Human Interferon Type II/BIOSYNTHESIS/PHARMACOLOGY Interleukin-1/PHARMACOLOGY Interleukin-2/*BIOSYNTHESIS/GENETICS/PHARMACOLOGY Interleukin-4/BIOSYNTHESIS/PHARMACOLOGY Interleukin-6/PHARMACOLOGY Lymphocyte Transformation/*DRUG EFFECTS Molecular Sequence Data Polymerase Chain Reaction Receptor-CD3 Complex, Antigen, T-Cell/IMMUNOLOGY Support, Non-U.S. Gov't Th1 Cells/CYTOLOGY Th2 Cells/CYTOLOGY JOURNAL ARTICLE
961030
M96A1413

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