IL-15 induces unspecific effector functions in human peptide-specific CD8+ T-cell cultures.
Antigen (Ag)-specific CD8+ T cells are a major host defence against viral infections. In the present study, we generated human CD8+ T-cell lines specific towards influenza matrix peptide (IMP)-pulsed Ag-presenting cells. We compared the effect of interleukin-2 (IL-2) and IL-15 on the proliferation and cytotoxic activity of primary and secondary IMP-specific cytotoxic T lymphocyte (CTL) culture. In primary CTL cultures, IL-15-induced cell expansion was considerably reduced as compared with IL-2-induced cell expansion, and IL-15 favoured the outgrowth of CTLs without peptide specificity in these cultures. Secondary IMP-specific CD8+ T cells were generated by the addition of IL-2 during two cycles of restimulation. From the third restimulation, identical CTL cultures were expanded with either IL-2 or IL-15 in parallel. Cell expansion as well as Ag specificity was considerably reduced after a 5 day culture period in the presence of IL-15. No or low CD69 expression was observed in IL-15-cultured CTLs, whereas IL-2-cultured CTLs contained high fractions of CD69+ cells. Furthermore, a high fraction of these latter cells coexpressed the cytotoxic marker CD56. However, IL-15-cultured CTLs exhibited cytotoxic activity without detectable expression of CD56, suggesting that CD56 is not essential for cytotoxic activity. Thus, the results presented suggest that IL-15 favours the outgrowth of unspecific cytotoxic effector T cells.
Lyngstrand
S T
ST
Institute of Medical Anatomy, Department A, The Panum Institute, University of Copenhagen, Copenhagen, Denmark.
Würtzen
P A
PA
Ødum
N
N
Nissen
M H
MH
Röpke
C
C
D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D000956:Antigens, Viral / Q000276:immunology; D017209:Apoptosis; D019002:CD56 Antigen / Q000378:metabolism; D002455:Cell Division; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D006801:Humans; D019409:Interleukin-15 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D037181:Lectins, C-Type; D008213:Lymphocyte Activation; D010446:Peptide Fragments / Q000276:immunology*; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000276:immunology*; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000956:Antigens, Viral; D019002:CD56 Antigen; D016207:Cytokines; D019409:Interleukin-15; D007376:Interleukin-2; D037181:Lectins, C-Type; D010446:Peptide Fragments; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2; D014763:Viral Matrix Proteins; D000099192:CD69 Antigens; C508024:IL15RA protein, human; C448634:influenza matrix peptide (58-66)