Differential modulation of LAK and ADCC functions of natural killer cells from AK-5 tumor-bearing rats by IL-2, IL-12 and IFN-gamma.
Modulation of NK cell activity by various lymphokines is well documented. Freshly isolated NK cells exhibit natural cytotoxicity (NC) and antibody-dependent cellular cytotoxicity (ADCC) against certain targets. Upon stimulation with IL-2, the NK cells acquire lymphokine-activated killer (LAK) activity, which enables them to kill a wide variety of targets. Our results demonstrate that freshly isolated NK cells from tumor-bearing rats exhibit NK activity towards YAC-1, and ADCC activity towards AK-5 targets. Fresh NK cells did not lyse AK-5 targets in the absence of anti AK-5 antibody. However, in vitro culture of fresh NK cells in the presence of rat recombinant IL-2 (r-IL-2) over a period of 7 days resulted in complete loss of ADCC activity with concomitant acquisition of LAK activity on AK-5 tumor targets. The LAK and ADCC activities could be effectively distinguished based on our observation that monoclonal anti-rat ICAM-1 and anti-rat LFA-1 antibodies inhibited only LAK activity, but not ADCC activity, in addition, anti-AK-5 antiserum, but not purified anti-AK-5 antibody, inhibited LAK activity, suggesting that soluble ICAM-1 present in hyperimmune serum could be responsible for inhibition of LAK activity. The loss of ADCC activity upon culture of NK cells with rIL-2 was not observed when the cultures were grown on a macrophage feeder layer. In addition, NK cells retained their ADCC activity when cultures were supplemented with a combination of recombinant IL-2 and IL-12. However IL-2, IFN-gamma or IL-12 alone did not prevent the loss of ADCC activity, suggesting the requirement of a combination of these lymphokines for the maintainance of ADCC activity.
Muralikrishna
K
K
Centre for Cellular and Molecular Biology, Hyderabad, India.
Varalakshmi
C
C
Khar
A
A
D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects*; D003602:Cytotoxicity, Immunologic; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D018664:Interleukin-12 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects* / Q000276:immunology*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D008222:Lymphokines / Q000494:pharmacology*; D008297:Male; D009365:Neoplasm Regression, Spontaneous / Q000276:immunology; D009374:Neoplasms, Experimental / Q000276:immunology*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins
D007376:Interleukin-2; D016169:Lymphocyte Function-Associated Antigen-1; D008222:Lymphokines; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1; D018664:Interleukin-12; D007371:Interferon-gamma