Differential role of signal 3 inflammatory cytokines in regulating CD8 T cell expansion and differentiation in vivo.
Following an infection, naïve CD8 T cells are stimulated by dendritic cells displaying pathogen-derived peptides on MHC-class I molecules (signal 1) and costimulatory molecules (signal 2). Additionally, pathogen-induced inflammatory cytokines also act directly on the responding CD8 T cells...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2011-02-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fimmu.2011.00004/full |
| _version_ | 1818980022609772544 |
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| author | Nhat-Long ePham Vladimir eBadovinac John eHarty John eHarty |
| author_facet | Nhat-Long ePham Vladimir eBadovinac John eHarty John eHarty |
| author_sort | Nhat-Long ePham |
| collection | DOAJ |
| description | Following an infection, naïve CD8 T cells are stimulated by dendritic cells displaying pathogen-derived peptides on MHC-class I molecules (signal 1) and costimulatory molecules (signal 2). Additionally, pathogen-induced inflammatory cytokines also act directly on the responding CD8 T cells to regulate their expansion and differentiation. In particular, both type I interferons (IFNs) and IL-12 have been described as critical survival signals (signal 3) for optimal CD8 T cell accumulation during the expansion phase. Furthermore, expansion in numbers of antigen-specific CD8 T cells is coupled with their acquisition of effector functions to combat the infection. However, it still remains unclear whether these same cytokines also regulate the effector/memory differentiation program of the CD8 T cell response in vivo. Here, we demonstrate that defective signaling by either type I IFNs or IL-12 to the responding CD8 T cells impairs maximal expansion in response to DC immunization + CpG ODN, but neither of these cytokines is essential to regulate the effector/memory differentiation program. In addition, lack of direct IL-12 signaling to CD8 T cells accelerates the development of central memory phenotype in both primary and secondary antigen-specific memory CD8 T cells. |
| first_indexed | 2024-12-20T17:08:49Z |
| format | Article |
| id | doaj.art-c88e7417cfc6472297cc92fcc14381dc |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-20T17:08:49Z |
| publishDate | 2011-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-c88e7417cfc6472297cc92fcc14381dc2022-12-21T19:32:12ZengFrontiers Media S.A.Frontiers in Immunology1664-32242011-02-01210.3389/fimmu.2011.000048891Differential role of signal 3 inflammatory cytokines in regulating CD8 T cell expansion and differentiation in vivo.Nhat-Long ePham0Vladimir eBadovinac1John eHarty2John eHarty3University of IowaUniversity of IowaUniversity of IowaUniversity of IowaFollowing an infection, naïve CD8 T cells are stimulated by dendritic cells displaying pathogen-derived peptides on MHC-class I molecules (signal 1) and costimulatory molecules (signal 2). Additionally, pathogen-induced inflammatory cytokines also act directly on the responding CD8 T cells to regulate their expansion and differentiation. In particular, both type I interferons (IFNs) and IL-12 have been described as critical survival signals (signal 3) for optimal CD8 T cell accumulation during the expansion phase. Furthermore, expansion in numbers of antigen-specific CD8 T cells is coupled with their acquisition of effector functions to combat the infection. However, it still remains unclear whether these same cytokines also regulate the effector/memory differentiation program of the CD8 T cell response in vivo. Here, we demonstrate that defective signaling by either type I IFNs or IL-12 to the responding CD8 T cells impairs maximal expansion in response to DC immunization + CpG ODN, but neither of these cytokines is essential to regulate the effector/memory differentiation program. In addition, lack of direct IL-12 signaling to CD8 T cells accelerates the development of central memory phenotype in both primary and secondary antigen-specific memory CD8 T cells.http://journal.frontiersin.org/Journal/10.3389/fimmu.2011.00004/fullCD8 T cellsinflammatory cytokineseffector/memory differentiationsignal 3 |
| spellingShingle | Nhat-Long ePham Vladimir eBadovinac John eHarty John eHarty Differential role of signal 3 inflammatory cytokines in regulating CD8 T cell expansion and differentiation in vivo. Frontiers in Immunology CD8 T cells inflammatory cytokines effector/memory differentiation signal 3 |
| title | Differential role of signal 3 inflammatory cytokines in regulating CD8 T cell expansion and differentiation in vivo. |
| title_full | Differential role of signal 3 inflammatory cytokines in regulating CD8 T cell expansion and differentiation in vivo. |
| title_fullStr | Differential role of signal 3 inflammatory cytokines in regulating CD8 T cell expansion and differentiation in vivo. |
| title_full_unstemmed | Differential role of signal 3 inflammatory cytokines in regulating CD8 T cell expansion and differentiation in vivo. |
| title_short | Differential role of signal 3 inflammatory cytokines in regulating CD8 T cell expansion and differentiation in vivo. |
| title_sort | differential role of signal 3 inflammatory cytokines in regulating cd8 t cell expansion and differentiation in vivo |
| topic | CD8 T cells inflammatory cytokines effector/memory differentiation signal 3 |
| url | http://journal.frontiersin.org/Journal/10.3389/fimmu.2011.00004/full |
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