NATURAL-KILLER AND LYMPHOKINE-ACTIVATED KILLER ACTIVITY IN HLA-B8,DR3-POSITIVE SUBJECTS

The haplotype HLA-BS,DRS is overrepresented in several autoimmune dise ases, implying that genes predisposing people to these disorders are l inked to this haplotype. In these diseases, various dysfunctions refle cting an impairment of the immune system have been found. Several repo rts indicate also that in HLA-B8,DR3-positive healthy subjects similar disorders may be demonstrated. In the present work, we have evaluated NK and LAK activity in these subjects. The study has been performed o n monocyte-depleted peripheral blood MNCs by using the K-562 cell line as a target for NK activity and the HL-60 cell line for as a target L AK activity. LAK cells were obtained by incubating MNCs for 3 days wit h 100 U/ml of rIL-2. The results of our experiments demonstrate that N K cell activity is significantly decreased in healthy subjects bearing the HLA-B8,DR3 haplotype. Since the number of circulating CD16(+) cel ls is not significantly different between HLA-B8,DR3-positive subjects and negative ones, it is unlikely that this defect is due to a decrea sed number of NK cells in effector cell preparations. The observation that the treatment with rIL-2 can restore the killer activity of MNCs from these subjects suggests instead that the reduced NK activity may be due at least in part to the imbalance of cytokine network that has been demonstrated in HLA-B8,DR3-positive subjects. Finally, since a de creased NK activity has been reported in the autoimmune diseases linke d to this haplotype, our results support the suggestion that immunolog ic changes observed in autoimmune diseases reflect systemic regulatory disorders that have a genetic basis.