50 Years Ago in The Journal of Pediatrics:

Article Outline

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Vaughan J, Greenberg SD. J Pediatr 1962;60:177-82

This study of the histological characteristics of “atypical lymphocytes” seen in the blood smears of 20 pediatric outpatients, as well as speculation on origin of the cells (thought to be “lymphocytes in the process of maturing to histiocytes or monocytes”) and nature of the stimulus (viral infection), added some specificity to the passing observations of blood smears by clinical pathologists. At the time, “infectious mononucleosis” was thought to be a viral infection, and the presence of serum heterophil antibodies was confirmatory. The absence of heterophil antibody in the infants and toddlers studied (90% of whom were aged <2 years) puzzled the investigators as to the cause of atypical lymphocytosis.

The discovery of Epstein-Barr virus as the primary etiology of infectious mononucleosis, as well as the absence of heterophil antibodies in Epstein-Barr virus–infected young children (and also in individuals with infectious mononucleosis due to cytomegalovirus), helped solve Vaughan and Greenberg’s puzzle. We now know that “atypical lymphocytes” are activated T lymphocytes. A brisk atypical lymphocytosis (10%-35% of white blood cells) is highly associated with Epstein-Barr virus and cytomegalovirus infection, and lower levels are common in children with viral respiratory tract infections and intracellular bacterial infections (eg, salmonellosis).