Heterosubtypic immunity to influenza A virus infection requires B cells but not CD8+ cytotoxic T lymphocytes

Academic Article


  • Heterosubtypic immunity (HSI), defined as protective cross-reactivity to lethal infection with influenza A virus of a serotype different from the virus initially encountered, is thought to be mediated by cross-reactive cytotoxic T lymphocytes (CTL). This study provides direct evidence for the role of effector CTL versus B cells in HSI in mice with a targeted disruption in the α chain of CD8 molecule (CD8+ T cell deficient) or the immunoglobulin μ heavy chain (B cell deficient), respectively. CD8+ T cell-deficient mice developed complete HSI. These mice displayed normal humoral immune responses, as determined by titers of subtype cross-reactive antibodies and virus-neutralizing antibodies specific for the immunizing influenza strain. In contrast, HSI was not observed in B cell-deficient mice, although these mice could mount cross-reactive CTL responses. These results show that B cells are required for HSI and provide new insight into the mechanisms of HSI, with significant implications in vaccine development.
  • Published In

    Digital Object Identifier (doi)

    Author List

  • Nguyen HH; van Ginkel FW; Vu HL; McGhee JR; Mestecky J
  • Start Page

  • 368
  • End Page

  • 376
  • Volume

  • 183
  • Issue

  • 3