Induction of CD4(+) T-cell-independent immunoglobulin responses by inactivated influenza virus.
Through cognate interaction between antigen-specific B-cell and CD4(+) alphabeta T cells, the CD4(+) alphabeta T cells secrete cytokines that initiate immunoglobulin (Ig) class switching from IgM to IgG. In this study, we show that formalin-inactivated influenza PR8 virus induces virus-specific IgM and IgG responses in the absence of CD4(+) T cells and that all four subclasses of IgG are produced. The immunized CD4-deficient mice were also found to be completely protected against lethal infection with live, pathogenic influenza virus. The ability of CD4(+) T-cell-deficient mice to generate these IgG responses was not found to be impaired when these mice were depleted of CD8(+) T cells with an anti-CD8 monoclonal antibody. In contrast, alphabeta T-cell-deficient mice (TCRbeta(-/-)) were not found to produce significant amounts of IgG upon immunization with formalin-inactivated PR8 virus. These results suggest that CD4(-) CD8(-) double-negative alphabeta T cells are playing a role in regulating Ig class switching in the absence of CD4(+) T cells.
Sha
Z
Z
Department of Microbiology and Immunology, Emory University, Atlanta, Georgia 30322, USA.
Compans
R W
RW
D000367:Age Factors; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D015704:CD4 Antigens / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D002642:Chick Embryo; D004285:Dogs; D005557:Formaldehyde / Q000494:pharmacology; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D009980:Influenza A virus / Q000187:drug effects / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology* / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009500:Neutralization Tests; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D013154:Spleen / Q000166:cytology
D000914:Antibodies, Viral; D015704:CD4 Antigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D016693:Receptors, Antigen, T-Cell, alpha-beta; D005557:Formaldehyde