Human Tc1 and Tc2/Tc0 CD8 T-cell clones display distinct cell surface and functional phenotypes.
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)
Vukmanovic-Stejic
M
M
Department of Immunology, Guy's, King's, and St. Thomas' School of Medicine, Rayne Institute, London, United Kingdom.
Vyas
B
B
Gorak-Stolinska
P
P
Noble
A
A
Kemeny
D M
DM
D015703:Antigens, CD / Q000032:analysis / Q000096:biosynthesis*; D017209:Apoptosis / Q000187:drug effects; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D002454:Cell Differentiation; D002999:Clone Cells; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis*; D003602:Cytotoxicity, Immunologic; D053222:Fas Ligand Protein; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D018664:Interleukin-12 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012016:Reference Values; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D015703:Antigens, CD; D016207:Cytokines; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D018664:Interleukin-12; D015847:Interleukin-4; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate