tetano
Editor, Senior Moderator
J Virol. 2014 Apr 23. [Epub ahead of print]
Roles of major histocompatibility complex class II in inducing protective immune responses to influenza vaccination.
Eunju O1, Lee YT, Ko EJ, Kim KH, Lee YN, Song JM, Kwon YM, Kim MC, Perez DR, Kang SM.
Author information
Abstract
Major histocompatibility complex class II-deficient (MHCII KO, A beta-/-) mice were used to assess the roles of MHC II molecules in inducing protective immune responses to vaccination. After vaccination with influenza A/PR8 virus-like particle (VLP) vaccine, in vivo and in vitro vaccine antigen specific IgG isotype antibodies were not detected in MHCII KO mice, which is quite different from CD4 T cell deficient mice that induced vaccine specific IgG antibodies. The deficiency of MHCII did not significantly affect the induction of antigen specific IgM antibody in sera. MHCII KO mice that were vaccinated with influenza VLP, whole inactivated influenza virus, or live attenuated influenza virus vaccines were not protected against lethal infection with influenza A/PR8 virus. Adoptive transfer of fractionated spleen cells from wild type mice to MHCII KO mice indicated that CD43+ cell populations with MHCII contributed more significantly to producing vaccine specific IgG antibodies than CD43-B220+ conventional B cell or CD4 T cell populations as well as conferring protection against lethal infection. Bone marrow derived dendritic cells from MHCII KO mice showed a significant defect in producing interleukin-6 and tumor necrosis factor α cytokines. Thus, results in this study provide evidence that MHC II molecules are playing multiple roles in inducing protective immunity to influenza vaccination.
IMPORTANCE:
In a conventional concept, major histocompatibility complex class II (MHCII) has been known to activate CD4 T helper immune cells. Deficiency of MHCII was considered to be equivalent to the lack of CD4 T cells in developing host immune responses to pathogens. However, roles of MHCII in inducing protective immune responses to vaccination have not been well understood. In this present study, we demonstrated that MHCII deficient mice showed much more significant defects in inducing protective antibody responses to influenza vaccination than CD4 T deficient mice. Further analysis showed that CD43 marker positive immune cells with MHCII as well as an innate immune simulating adjuvant could rescue some defects in inducing protective immune responses in MHCII deficient mice. These results in this study indicate important implications in understanding host immune inducing mechanisms to vaccination as well as in developing effective vaccines and adjuvants.
PMID:
24760891
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24760891
Roles of major histocompatibility complex class II in inducing protective immune responses to influenza vaccination.
Eunju O1, Lee YT, Ko EJ, Kim KH, Lee YN, Song JM, Kwon YM, Kim MC, Perez DR, Kang SM.
Author information
Abstract
Major histocompatibility complex class II-deficient (MHCII KO, A beta-/-) mice were used to assess the roles of MHC II molecules in inducing protective immune responses to vaccination. After vaccination with influenza A/PR8 virus-like particle (VLP) vaccine, in vivo and in vitro vaccine antigen specific IgG isotype antibodies were not detected in MHCII KO mice, which is quite different from CD4 T cell deficient mice that induced vaccine specific IgG antibodies. The deficiency of MHCII did not significantly affect the induction of antigen specific IgM antibody in sera. MHCII KO mice that were vaccinated with influenza VLP, whole inactivated influenza virus, or live attenuated influenza virus vaccines were not protected against lethal infection with influenza A/PR8 virus. Adoptive transfer of fractionated spleen cells from wild type mice to MHCII KO mice indicated that CD43+ cell populations with MHCII contributed more significantly to producing vaccine specific IgG antibodies than CD43-B220+ conventional B cell or CD4 T cell populations as well as conferring protection against lethal infection. Bone marrow derived dendritic cells from MHCII KO mice showed a significant defect in producing interleukin-6 and tumor necrosis factor α cytokines. Thus, results in this study provide evidence that MHC II molecules are playing multiple roles in inducing protective immunity to influenza vaccination.
IMPORTANCE:
In a conventional concept, major histocompatibility complex class II (MHCII) has been known to activate CD4 T helper immune cells. Deficiency of MHCII was considered to be equivalent to the lack of CD4 T cells in developing host immune responses to pathogens. However, roles of MHCII in inducing protective immune responses to vaccination have not been well understood. In this present study, we demonstrated that MHCII deficient mice showed much more significant defects in inducing protective antibody responses to influenza vaccination than CD4 T deficient mice. Further analysis showed that CD43 marker positive immune cells with MHCII as well as an innate immune simulating adjuvant could rescue some defects in inducing protective immune responses in MHCII deficient mice. These results in this study indicate important implications in understanding host immune inducing mechanisms to vaccination as well as in developing effective vaccines and adjuvants.
PMID:
24760891
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24760891