Natural killer (NK) cells recognize the absence of self MHC class I as a way to discriminate normal cells from cells in distress. In humans, this "missing self" recognition is ensured by inhibitory receptors such as KIR, which dampen NK cell activation upon interaction with their MHC class I ligands. We show here that NK cells lacking inhibitory KIR for self MHC class I molecules are present in human peripheral blood. These cells harbor a mature NK cell phenotype but are hyporesponsive to various stimuli, including MHC class I-deficient target cells. This response is in contrast to NK cells that express a single inhibitory KIR specific for self MHC class I, which are functionally competent when exposed to the same stimuli. These results show the involvement of KIR-MHC class I interactions in the calibration of NK cell effector capacities, suggesting its role in the subsequent "missing self" recognition.

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Objective. To test whether the G-to-A polymorphism at position-308 in the promoter of the tumor necrosis factor ␣ (TNF␣) gene influences response to infliximab therapy in patients with rheumatoid arthritis (RA). Methods. We genotyped 59 RA patients by polymerase chain reaction and subdivided them into two groups: those with the A/A or A/G genotype and those with the G/G genotype. We compared the groups' clinical responses to infliximab treatment after 22 weeks, using the Disease Activity Score in 28 joints (DAS28). Results. We found that 42% of patients in the A/A and A/G group and 81% of patients in the G/G group had improvement of at least 1.2 in the DAS28 score (P ‫؍‬ 0.0086). The average improvement in the DAS28 score was 1.24 in the A/A and A/G patients and 2.29 in the G/G patients (P ‫؍‬ 0.029). Conclusion. These data suggest that patients with a TNF␣-308G/G genotype are better infliximab responders than are patients with A/A or A/G genotypes. TNF␣ ؊308 genotyping may be a useful tool for predicting response to infliximab treatment. PATIENTS AND METHODS Patients. Fifty-nine consecutive RA patients requiring infliximab therapy were included in this prospective study. All of them were enrolled in the Department of Rheumatology at La Conception Hospital in Marseille from September 2000 to January 2002. All patients fulfilled the American College of Rheumatology (formerly, the American Rheumatism Association) 1987 revised criteria for RA (8), and all had evidence of active disease, as indicated by a Disease Activity Score in 28 joints (DAS28) (9) of Ͼ3.2 despite methotrexate (MTX)