Serum antibodies critically affect virus-specific CD4+/CD8+ T cell balance during respiratory syncytial virus infections.

Abstract

Following infection with respiratory syncytial virus (RSV), reinfection in healthy individuals is common and presumably due to ineffective memory T cell responses. In peripheral blood of healthy adults, a higher CD4(+)/CD8(+) memory T cell ratio was observed compared with the ratio of virus-specific effector CD4(+)/CD8(+) T cells that we had found in earlier work during primary RSV infections. In mice, we show that an enhanced ratio of RSV-specific neutralizing to nonneutralizing Abs profoundly enhanced the CD4(+) T cell response during RSV infection. Moreover, FcγRs and complement factor C1q contributed to this Ab-mediated enhancement. Therefore, the increase in CD4(+) memory T cell response likely occurs through enhanced endosomal Ag processing dependent on FcγRs. The resulting shift in memory T cell response was likely amplified by suppressed T cell proliferation caused by RSV infection of APCs, a route important for Ag presentation via MHC class I molecules leading to CD8(+) T cell activation. Decreasing memory CD8(+) T cell numbers could explain the inadequate immunity during repeated RSV infections. Understanding this interplay of Ab-mediated CD4(+) memory T cell response enhancement and infection mediated CD8(+) memory T cell suppression is likely critical for development of effective RSV vaccines.

• Authors: Debby Kruijsen, Mark J Bakkers, Nathalie O van Uden, Marco C Viveen, Tetje C van der Sluis, Jan L Kimpen, Jeanette H Leusen, Frank E Coenjaerts, Grada M van Bleek
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 185 Issue 11 Pg. 6489-98 (Dec 01 2010) ISSN: 1550-6606 [Electronic] United States
• PMID: 20971927 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Viral
• Epitopes, T-Lymphocyte

Topics

• Adaptive Immunity
• Animals
• Antibodies, Viral (blood)
• Antigen Presentation (immunology)
• CD4-Positive T-Lymphocytes (immunology, pathology, virology)
• Cells, Cultured
• Dendritic Cells (immunology, pathology, virology)
• Epitopes, T-Lymphocyte (immunology)
• Humans
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• NIH 3T3 Cells
• Respiratory Syncytial Virus Infections (immunology, pathology)
• Respiratory Syncytial Viruses (immunology)