Human Tc1 and Tc2/Tc0 CD8 T-cell clones display distinct cell surface and functional phenotypes.

Important note: Information in this article was accurate in 2000. The state of the art may have changed since the publication date.

Human Tc1 and Tc2/Tc0 CD8 T-cell clones display distinct cell surface and functional phenotypes.

Blood. 2000 Jan 1;95(1):231-40. Unique Identifier : AIDSLINE MED/20076262
Vukmanovic-Stejic M; Vyas B; Gorak-Stolinska P; Noble A; Kemeny DM; Department of Immunology, Guy's, King's, and St. Thomas' School; of Medicine, Rayne Institute, London, United Kingdom.

Abstract: It has recently become clear that distinct subsets of CD8 T cells, analogous to their CD4 counterparts, exist in rodents and humans. To examine functional differences between human CD8 T-cell subsets, we generated Tc1, Tc2, and Tc0 T-cell clones from the peripheral blood of healthy individuals. The majority of CD8 T-cell clones generated displayed a classic Tc1 phenotype, but 10% to 20% secreted interleukin (IL)-4 in addition to interferon-gamma (Tc0 phenotype). Generation of Tc2 clones was dependent on the use of anti-CD3 and anti-CD28 as the primary stimulus. The cytokine profiles of established clones remained susceptible to modification by the addition of IL-12 and IL-4. In addition, IL-12 enhanced and IL-4 inhibited the growth of Tc1 but not Tc2/0 CD8 T-cell clones. Significant functional differences were observed between the subsets. Tc2/0 clones expressed CD30 and CD40 ligand at a much higher level than Tc1 clones. Both Tc1 and Tc2/0 clones showed comparable cytotoxicity and produced similar levels of perforin and Fas L. However, Tc2 clones were much more resistant to activation-induced cell death and less susceptible to apoptosis by direct Fas ligation. Moreover, Tc1 and Tc2 clones had opposing effects on the development of CD4 effectors, promoting type 1 and type 2 responses, respectively. These data provide evidence for profound differences between human CD8 T-cell subsets that may be important in their functions as cytotoxic or immunoregulatory cells. (Blood. 2000;95:231-240)

Keywords: JOURNAL ARTICLE Antigens, CD/ANALYSIS/*BIOSYNTHESIS Apoptosis/DRUG EFFECTS Cell Differentiation Clone Cells Coculture Cytokines/*BIOSYNTHESIS Cytotoxicity, Immunologic CD4-CD8 Ratio CD4-Positive T-Lymphocytes/CYTOLOGY/*IMMUNOLOGY CD8-Positive T-Lymphocytes/*CYTOLOGY/DRUG EFFECTS/*IMMUNOLOGY Flow Cytometry Human Immunophenotyping Interleukin-12/PHARMACOLOGY Interleukin-4/PHARMACOLOGY Ionomycin/PHARMACOLOGY Lymphocyte Transformation Membrane Glycoproteins/BIOSYNTHESIS Reference Values Support, Non-U.S. Gov't Tetradecanoylphorbol Acetate/PHARMACOLOGY

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