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.
Original language | English |
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Pages (from-to) | 6489-6498 |
Number of pages | 10 |
Journal | Journal of Immunology |
Volume | 185 |
Issue number | 11 |
DOIs | |
Publication status | Published - 1 Dec 2010 |
Keywords
- Adaptive Immunity
- Animals
- Antibodies, Viral
- Antigen Presentation
- CD4-Positive T-Lymphocytes
- Cells, Cultured
- Dendritic Cells
- Epitopes, T-Lymphocyte
- Humans
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- NIH 3T3 Cells
- Respiratory Syncytial Virus Infections
- Respiratory Syncytial Viruses
- Journal Article
- Research Support, Non-U.S. Gov't