A 3-month-old girl, the first child of consanguineous parents with a family history of unexplained febrile episodes including a death from infection of the eldest brother of the father at 8 months of age, was admitted to our hospital for gastroenteritis. She had a mild leukocytosis (27.4 109/L) that was due mainly to an increased number of lymphocytes. After oral rehydration, the child recovered rapidly, and she was discharged after the fever had disappeared. We subsequently learned from the laboratory data that the clinical symptoms had been caused by cytomegalovirus (CMV). In addition, we found that the lymphocyte subsets causing the leukocytosis were extremely unbalanced; 90% were CD56dim natural killer (NK) cells, 10% were B cells, while T cells were virtually absent (0.07 109/L). Genetic analysis showed early stop codons in the patient’s genes encoding the-chain of the interleukin-7 (IL-7) receptor, a defect known to be associated with this particular TB NK SCID-phenotype. 1, 2

The correlation between viral load, number of NK cells, and cytokine serum-levels during the follow up was very suggestive of a causal relation (Figure 1A-C). The extremely high number of NK cells (23.8 109/L) present at the peak of viremia (4.1 104 copies CMV-DNA/mL of serum) remained elevated for approximately 2weeks. At that moment, NKcell–derived3 cytokines granulocyte macrophage–colony stimulating factor (GM-CSF) and interferon-(IFN-) and the ensuing IFN-inducible protein-10 were at very high levels (Figure 1B, C). The viral load, already reduced by one log, decreased further to 150 copies/mL at 4 to 5 weeks and could not be detected anymore after the 6th week. By then, the number of NK cells had dropped to 2 109/L and the cytokines had returned to normal levels (Figure 1B, C, gray bars). The phenotype of the NK cells expanded at the peak of infection had several interesting features (Figure 1D). Half the population