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T Cells1
,
*
Molecular Immunology Laboratory, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20852;
Laboratory of Viral Diseases, Cellular Biology Section and Viral Immunology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and
Department of Microbiology and Immunology, Indiana University School of Medicine, Walther Oncology Center, Indianapolis, IN 46202
The mechanisms of broad cross-protection to influenza
viruses of different subtypes, termed heterosubtypic immunity, remain
incompletely understood. We used knockout mouse strains to examine the
potential for heterosubtypic immunity in mice lacking IgA, all Ig and B
cells, NKT cells (CD1 knockout mice), or 
T cells. Mice were
immunized with live influenza A virus and compared with controls
immunized with unrelated influenza B virus. IgA-/- mice
survived full respiratory tract challenge with heterosubtypic virus
that was lethal to controls. IgA-/- mice also cleared
virus from the nasopharynx and lungs following heterosubtypic challenge
limited to the upper respiratory tract, where IgA has been shown to
play an important role. Ig-/- mice controlled the
replication of heterosubtypic challenge virus in the lungs. Acute
depletion of CD4+ or CD8+ T cell subsets
abrogated this clearance of virus, thus indicating that both
CD4+ and CD8+ T cells are required for
protection in the absence of Ig. These results in Ig-/-
mice indicate that CD4+ T cells can function by mechanisms
other than providing help to B cells for the generation of Abs. Like
wild-type mice, CD1-/- mice and -/-
mice survived lethal heterosubtypic challenge. Acute depletion of
CD4+ and CD8+ cells abrogated heterosubtypic
protection in -/- mice, but not B6 controls,
suggesting a contribution of T cells. Our results demonstrate
that the Ab and cellular subsets deficient in these knockout mice are
not required for heterosubtypic protection, but each may play a role in
a multifaceted response that as a whole is more effective than any of
its parts.
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