Heterosubtypic immunity to influenza A virus infection requires B cells but not CD8+ cytotoxic T lymphocytes.
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 alpha chain of CD8 molecule (CD8(+) T cell deficient) or the immunoglobulin mu 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.
Nguyen
H H
HH
Department of Microbiology and Immunobiology Vaccine Center, University of Alabama at Birmingham, Birmingham, AL 35294-2170, USA. nghuan@uab.edu
van Ginkel FW
Vu
H L
HL
McGhee
J R
JR
Mestecky
J
J
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology*; D016827:CD8 Antigens / Q000235:genetics; D002460:Cell Line; D003429:Cross Reactions; D016207:Cytokines / Q000096:biosynthesis; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D017353:Gene Deletion; D005803:Genes, Immunoglobulin; D006801:Humans; D007114:Immunization; D007148:Immunoglobulin mu-Chains / Q000235:genetics; D009980:Influenza A virus / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology* / Q000401:mortality / Q000821:virology; D008168:Lung / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000914:Antibodies, Viral; D016827:CD8 Antigens; D016207:Cytokines; D007148:Immunoglobulin mu-Chains