Reduction of Natural Killer but Not Effector CD8 T Lymphoyctes in Three Consecutive Cases of Severe/Lethal H1N1/09 Influenza A Virus Infection

Abstract

BackgroundThe cause of severe disease in some patients infected with pandemic influenza A virus is unclear.Methodology/Principal FindingsWe present the cellular immunology profile in the blood, and detailed clinical (and post-mortem) findings of three patients with rapidly progressive infection, including a pregnant patient who died. The striking finding is of reduction in natural killer (NK) cells but preservation of activated effector CD8 T lymphocytes; with viraemia in the patient who had no NK cells. Comparison with control groups suggests that the reduction of NK cells is unique to these severely ill patients.Conclusion/SignificanceOur report shows markedly reduced NK cells in the three patients that we sampled and raises the hypothesis that NK may have a more significant role than T lymphocytes in controlling viral burden when the host is confronted with a new influenza A virus subtype.

Influenza Virus Infection but Not H1N1 Influenza Virus Immunization Is Associated with Changes in Peripheral Blood NK Cell Subset Levels

“…In addition, it is possible that the changes in the levels of NK lymphocytes may reflect nonspecific effects of a systemic inflammatory process rather than a specific response to influenza virus. However, our results are in apparent contradiction with those of previous reports showing diminished levels of NK cells in patients with influenza infection (18,19). It is feasible that the times of blood sampling, the degrees of disease severity, the virus strains involved, and the genetic backgrounds of the patients studied may account, at least in part, for these contrasting results.…”

“…Over the past decade, several studies have addressed the role of NK cells and their receptors involved in the induction of cell killing in influenza virus infections (8,9,10,12,15,19,22,23). Because NK lymphocytes do not require prior sensitization to exert their lytic effects on infected cells, they may have a key protective role against emergent pathogens or new variants or strains of different viruses.…”

“…Furthermore, it has been found that the decreased NK cell activity induced by influenza infection may contribute to bacterial superinfections (17). Studies performed on patients with 2009 pandemic influenza A(H1N1) infection showed a reduction in NK cells in peripheral blood samples (18,19). Thus, influenza infection seems to be associated with significant changes in the number and activity of NK cells.…”

Influenza, Immune System, and Pregnancy

“…Among patients severely ill after H1N1/09 infection, reduction in NK cells, but preservation of T lymphocytes, was observed. 86 The NK cells are present in maternal decidua in large numbers where they can destroy virus-infected cells via a perforin-dependent mechanism, leading to apoptosis induction. 36 …”

Characterization of the Human CD8+T Cell Response following Infection with 2009 Pandemic Influenza H1N1 Virus

“…The rapid decrease of virus-specific CD8 ϩ T cells from the blood may reflect migration of these cells to the site of infection (12). It has been reported that the frequency of Tm ϩ CD8 ϩ T cell is low after 2009 H1N1 influenza virus infection (6). However, T cell responses were analyzed with Tm in two patients only and at a late time point after the onset of clinical symptoms.…”