Serum antibodies critically affect virus-specific CD4+/CD8+ T cell balance during respiratory syncytial virus infections.
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.
Kruijsen
Debby
D
Department of Pediatrics, Wilhelmina Children's Hospital, Utrecht, The Netherlands.
Bakkers
Mark J
MJ
van Uden
Nathalie O
NO
Viveen
Marco C
MC
van der Sluis
Tetje C
TC
Kimpen
Jan L
JL
Leusen
Jeanette H
JH
Coenjaerts
Frank E
FE
van Bleek
Grada M
GM
D056704:Adaptive Immunity; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D017951:Antigen Presentation / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology / Q000821:virology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D041681:NIH 3T3 Cells; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000473:pathology; D012136:Respiratory Syncytial Viruses / Q000276:immunology*
D000914:Antibodies, Viral; D018984:Epitopes, T-Lymphocyte