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Antigen-Driven Expansion and Contraction of CD8⁺-Activated T Cells in Primary EBV Infection¹

Yo Hoshino^*,, Tsuneo Morishima, Hiroshi Kimura, Kazuo Nishikawa, Tatsuya Tsurumi^* and Kiyotaka Kuzushima^2,*

^* Laboratory of Viral Oncology, Aichi Cancer Center Research Institute, Nagoya, Japan; Department of Pediatrics, Nagoya University School of Medicine, Nagoya, Japan; and Department of Pediatrics, Nagoya Ekisaikai Hospital, Nagoya, Japan

The origin of the increased numbers of CD8⁺ atypical lymphocytes, expressing activated markers such as HLA-DR or CD45RO, in the peripheral blood of patients with infectious mononucleosis (IM) has been debated. Using a recently developed assay to detect intracellular accumulation of IFN- in EBV-reactive T cells by FACS, we have demonstrated that 34–54% of HLA-DR⁺/CD8⁺ and 34–60% of CD45RO⁺/CD8⁺ T cells in the PBMCs of febrile patients suffering from IM are EBV-specific. The EBV-specific CD8⁺ T cell counts in the PBMCs of four febrile patients suffering from IM ranged between 2260 and 8200/µl, decreasing to 5.1% and 7.9% of the counts in the first samples over 10 days in two donors. The decline of CD8⁺ T cell subpopulations, namely HLA-DR⁺, CD45RO⁺, and EBV-specific T cells, was in parallel with the drop in the EBV genome load. These data indicate that the Ag-driven expansion of CD8⁺ T cells and subsequent contraction with the Ag decline in vivo in humans is effective for clearing virus-infected cells with minimal disturbance of the homeostasis of the immune system.

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