Comparative immunophenotypic features of EBV-positive and EBV-negative atypical lymphocytosis




Atypical lymphocytosis is a common peripheral blood abnormality seen not only in Epstein-Barr virus (EBV)-associated acute infectious mononucleosis but also in other conditions, including other viral infections, cancer, immune reactions, etc. Despite numerous reports of individual immunophenotypic alterations in EBV-positive infectious mononucleosis, a detailed comparative analysis of the immunophenotypic changes of peripheral blood lymphocyte subsets in infectious mononucleosis and other forms of atypical lymphocytosis is lacking.


Multiparametric flow immunocytometry with 26 monoclonal antibodies was performed on peripheral blood lymphocytes from 97 cases of atypical lymphocytosis and 37 normal controls. Atypical lymphocytosis was defined as absolute lymphocytosis with >10% atypical lymphocytes. Absolute or relative mean values of various lymphocyte subsets from EBV-positive cases, EBV-negative cases, and normal controls were compared with the Student's t-test.


Highly significant abnormalities detected in atypical lymphocytosis include increases in CD3+/CD8+, CD3−/CD16/56+, CD3+/γδ+, CD8+/CD48−, CD8+/CD57−, CD8+/CD95+, CD4+/CCR5+ CD4+/CD7−, CD4+/CD43−, CD4+/CD48−, and CD4+/CD62L− subsets. In contrast, no change in absolute CD4+ T cell and CD19+ B cell counts is seen. When compared with EBV-negative cases, EBV-positive cases are characterized by younger age, and increased numbers of absolute lymphocytes, atypical lymphocytes, CD8+ cells, NK cells, γδ T cells, CD8+/CD45RO+ cells, CD8+/CD57− cells, and CD8+/CD28+ cells.


All forms of atypical lymphocytosis are characterized by a marked increase in activated CD8-positive T cells, a moderate increase in NK cells, and no increase in CD4-positive T cells and B cells. Although morphologically indistinguishable, EBV-associated mononucleosis is characterized by several significant differences in peripheral blood lymphocyte subsets when compared with EBV-negative atypical lymphocytosis, most notably increased numbers of CD57-negative CD8 T cells and γδ T cells. Cytometry Part B (Clin. Cytometry) 55B:22–28, 2003. © 2003 Wiley-Liss, Inc.