A reduction in the number of peripheral CD28⁺ CD8⁺ T cells in the acute phase of influenza

Influenza patients show a high incidence of T lymphocytopenia in the acute phase of the illness. Since CD8⁺ T cells play an important role in influenza virus infection, we investigated which subset of CD8⁺ T cells was involved in this lymphocytopenia. CD8⁺ T cells from eight patients with influenza A were studied for lymphocyte count, surface marker, and intracellular IFN-γ production in the acute (days 1-3) and recovery phases (days 9-12). Total and T lymphocyte counts in the acute phase were approximately three times less than in the recovery phase; however, the CD4/8 ratio was the same in both phases. The cell count reduction in the acute phase was attributed predominantly to the CD28⁺ CD8⁺ subset, compared with the CD28^- CD8⁺ subset. The memory/activation marker CD45RO on the CD8⁺ T cells was assessed. The CD28⁺ CD45RO^- subset, a naive phenotype, was reduced significantly in number in the acute phase compared with the recovery phase. The CD28⁺ CD45RO⁺ subset, a memory phenotype, was also reduced in the acute phase, but the reduction was not statistically significant. Intracellular IFN-γ in the CD8⁺ subset after mitogenic stimulation was measured by flow cytometry; the percentage of CD28⁺ IFN-γ-/CD8⁺ subset in the acute phase was significantly less than in the recovery phase. These results indicated that the predominant reduction of peripheral CD8⁺ T cells in the acute phase of influenza was from naive-type lymphocytes, suggesting that these quantitative and qualitative changes of CD8⁺ T cells in influenza are important for understanding the immunological pathogenesis.