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

Journal of immunology (Baltimore, Md. : 1950) (2010-10-26)
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
ABSTRAKT

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.

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Sigma-Aldrich
Brefeldin A, from Penicillium brefeldianum, ≥99% (HPLC and TLC)
Sigma-Aldrich
Anti-RSV Antibody, glycoprotein, all type A, B strains, clone 131-2G, clone 131-2G, Chemicon®, from mouse
Millipore
Protein G Sepharose, Fast Flow, recombinant, expressed in E. coli, aqueous ethanol suspension