Host differences in influenza-specific CD4 T cell and B cell responses are modulated by viral strain and route of immunization.
The antibody response to influenza infection is largely dependent on CD4 T cell help for B cells. Cognate signals and secreted factors provided by CD4 T cells drive B cell activation and regulate antibody isotype switching for optimal antiviral activity. Recently, we analyzed HLA-DR1 transgenic (DR1...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3311631?pdf=render |
| _version_ | 1817985317370593280 |
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| author | Aarthi Sundararajan Lifang Huan Katherine A Richards Glendie Marcelin Shabnam Alam Hyemee Joo Hongmei Yang Richard J Webby David J Topham Andrea J Sant Mark Y Sangster |
| author_facet | Aarthi Sundararajan Lifang Huan Katherine A Richards Glendie Marcelin Shabnam Alam Hyemee Joo Hongmei Yang Richard J Webby David J Topham Andrea J Sant Mark Y Sangster |
| author_sort | Aarthi Sundararajan |
| collection | DOAJ |
| description | The antibody response to influenza infection is largely dependent on CD4 T cell help for B cells. Cognate signals and secreted factors provided by CD4 T cells drive B cell activation and regulate antibody isotype switching for optimal antiviral activity. Recently, we analyzed HLA-DR1 transgenic (DR1) mice and C57BL/10 (B10) mice after infection with influenza virus A/New Caledonia/20/99 (NC) and defined epitopes recognized by virus-specific CD4 T cells. Using this information in the current study, we demonstrate that the pattern of secretion of IL-2, IFN-γ, and IL-4 by CD4 T cells activated by NC infection is largely independent of epitope specificity and the magnitude of the epitope-specific response. Interestingly, however, the characteristics of the virus-specific CD4 T cell and the B cell response to NC infection differed in DR1 and B10 mice. The response in B10 mice featured predominantly IFN-γ-secreting CD4 T cells and strong IgG2b/IgG2c production. In contrast, in DR1 mice most CD4 T cells secreted IL-2 and IgG production was IgG1-biased. Infection of DR1 mice with influenza PR8 generated a response that was comparable to that in B10 mice, with predominantly IFN-γ-secreting CD4 T cells and greater numbers of IgG2c than IgG1 antibody-secreting cells. The response to intramuscular vaccination with inactivated NC was similar in DR1 and B10 mice; the majority of CD4 T cells secreted IL-2 and most IgG antibody-secreting cells produced IgG2b or IgG2c. Our findings identify inherent host influences on characteristics of the virus-specific CD4 T cell and B cell responses that are restricted to the lung environment. Furthermore, we show that these host influences are substantially modulated by the type of infecting virus via the early induction of innate factors. Our findings emphasize the importance of immunization strategy for demonstrating inherent host differences in CD4 T cell and B cell responses. |
| first_indexed | 2024-04-13T23:56:20Z |
| format | Article |
| id | doaj.art-2f05a7f4487b4e9f81c3a1af317f71ba |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T23:56:20Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-2f05a7f4487b4e9f81c3a1af317f71ba2022-12-22T02:23:53ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0173e3437710.1371/journal.pone.0034377Host differences in influenza-specific CD4 T cell and B cell responses are modulated by viral strain and route of immunization.Aarthi SundararajanLifang HuanKatherine A RichardsGlendie MarcelinShabnam AlamHyemee JooHongmei YangRichard J WebbyDavid J TophamAndrea J SantMark Y SangsterThe antibody response to influenza infection is largely dependent on CD4 T cell help for B cells. Cognate signals and secreted factors provided by CD4 T cells drive B cell activation and regulate antibody isotype switching for optimal antiviral activity. Recently, we analyzed HLA-DR1 transgenic (DR1) mice and C57BL/10 (B10) mice after infection with influenza virus A/New Caledonia/20/99 (NC) and defined epitopes recognized by virus-specific CD4 T cells. Using this information in the current study, we demonstrate that the pattern of secretion of IL-2, IFN-γ, and IL-4 by CD4 T cells activated by NC infection is largely independent of epitope specificity and the magnitude of the epitope-specific response. Interestingly, however, the characteristics of the virus-specific CD4 T cell and the B cell response to NC infection differed in DR1 and B10 mice. The response in B10 mice featured predominantly IFN-γ-secreting CD4 T cells and strong IgG2b/IgG2c production. In contrast, in DR1 mice most CD4 T cells secreted IL-2 and IgG production was IgG1-biased. Infection of DR1 mice with influenza PR8 generated a response that was comparable to that in B10 mice, with predominantly IFN-γ-secreting CD4 T cells and greater numbers of IgG2c than IgG1 antibody-secreting cells. The response to intramuscular vaccination with inactivated NC was similar in DR1 and B10 mice; the majority of CD4 T cells secreted IL-2 and most IgG antibody-secreting cells produced IgG2b or IgG2c. Our findings identify inherent host influences on characteristics of the virus-specific CD4 T cell and B cell responses that are restricted to the lung environment. Furthermore, we show that these host influences are substantially modulated by the type of infecting virus via the early induction of innate factors. Our findings emphasize the importance of immunization strategy for demonstrating inherent host differences in CD4 T cell and B cell responses.http://europepmc.org/articles/PMC3311631?pdf=render |
| spellingShingle | Aarthi Sundararajan Lifang Huan Katherine A Richards Glendie Marcelin Shabnam Alam Hyemee Joo Hongmei Yang Richard J Webby David J Topham Andrea J Sant Mark Y Sangster Host differences in influenza-specific CD4 T cell and B cell responses are modulated by viral strain and route of immunization. PLoS ONE |
| title | Host differences in influenza-specific CD4 T cell and B cell responses are modulated by viral strain and route of immunization. |
| title_full | Host differences in influenza-specific CD4 T cell and B cell responses are modulated by viral strain and route of immunization. |
| title_fullStr | Host differences in influenza-specific CD4 T cell and B cell responses are modulated by viral strain and route of immunization. |
| title_full_unstemmed | Host differences in influenza-specific CD4 T cell and B cell responses are modulated by viral strain and route of immunization. |
| title_short | Host differences in influenza-specific CD4 T cell and B cell responses are modulated by viral strain and route of immunization. |
| title_sort | host differences in influenza specific cd4 t cell and b cell responses are modulated by viral strain and route of immunization |
| url | http://europepmc.org/articles/PMC3311631?pdf=render |
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