Target cell induced activation of NK cells in vitro: cytokine production and enhancement of cytotoxic function.
This study examines the effect of fixed AK-5 tumour cells on rat NK cells. Co-culture of NK cells with fixed tumour cells augmented the cytotoxicity of NK cells against NK-sensitive targets, YAC-1 and AK-5, and induced the secretion of IFN-gamma by NK cells. Antibody against IFN-gamma suppressed the anti-tumour activity of NK cells, whereas the addition of T cells during co-culture enhanced this activity. However, macrophages and B cells had no significant effect when present during co-culture with NK cells. All the inducible cytotoxicity was contained within the NK (CD161+) and NKT (CD3+, CD161+) subsets of lymphocytes. However, in the presence of T cells, the cytolytic potential of NKT cells was higher than that of NK cells alone. The augmentation of cytotoxic activity of NK cells by AK-5 cells in presence of T cells was dependent on IL-2 and IFN-gamma secretion. NK cell activation was blocked by specific antibodies to IL-2 and IFN-gamma in the presence of T cells. Interaction between fixed AK-5 cells with NK and T cell populations induced the expression of Fas-L and perforin in NK cells. These data demonstrate that fixed AK-5 cells initiated cytokine synthesis by NK cells, and the enhanced cytotoxic activity in the presence of T cells was induced as a consequence of the products secreted by activated T lymphocytes. The present observations reflect the possible interactions taking place in vivo after the transplantation of AK-5 tumour in animals. They also suggest direct activation of NK cells after their interaction with the tumour cells.
Das
S
S
Centre for Cellular and Molecular Biology, Hyderabad, India.
Varalakshmi
C
C
Kumari
A L
AL
Patel
M
M
Khar
A
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015415:Biomarkers; D002478:Cells, Cultured / Q000276:immunology; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D053222:Fas Ligand Protein; D005805:Genes, MHC Class I; D006649:Histocompatibility Antigens / Q000096:biosynthesis / Q000276:immunology; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D014407:Tumor Cells, Cultured / Q000276:immunology
D000911:Antibodies, Monoclonal; D015415:Biomarkers; D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D006649:Histocompatibility Antigens; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger; C038353:histocompatibility antigens RT, rat; D054353:Perforin; D007371:Interferon-gamma