Cytokine diversity in the Th1-dominated human anti-influenza response caused by variable cytokine expression by Th1 cells, and a minor population of uncommitted IL-2+IFNγ- Thpp cells.
Within overall Th1-like human memory T cell responses, individual T cells may express only some of the characteristic Th1 cytokines when reactivated. In the Th1-oriented memory response to influenza, we have tested the contributions of two potential mechanisms for this diversity: variable expression...
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0095986&type=printable |
| _version_ | 1826587185098260480 |
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| author | Nan Deng Jason M Weaver Tim R Mosmann |
| author_facet | Nan Deng Jason M Weaver Tim R Mosmann |
| author_sort | Nan Deng |
| collection | DOAJ |
| description | Within overall Th1-like human memory T cell responses, individual T cells may express only some of the characteristic Th1 cytokines when reactivated. In the Th1-oriented memory response to influenza, we have tested the contributions of two potential mechanisms for this diversity: variable expression of cytokines by a uniform population during activation, or different stable subsets that consistently expressed subsets of the Th1 cytokine pattern. To test for short-term variability, in vitro-stimulated influenza-specific human memory CD4+ T cells were sorted according to IL-2 and IFNγ expression, cultured briefly in vitro, and cytokine patterns measured after restimulation. Cells that were initially IFNγ+ and either IL-2+ or IL-2- converged rapidly, containing similar proportions of IL-2-IFNγ+ and IL-2+IFNγ+ cells after culture and restimulation. Both phenotypes expressed Tbet, and similar patterns of mRNA. Thus variability of IL-2 expression in IFNγ+ cells appeared to be regulated more by short-term variability than by stable differentiated subsets. In contrast, heterogeneous expression of IFNγ in IL-2+ influenza-specific T cells appeared to be due partly to stable T cell subsets. After sorting, culture and restimulation, influenza-specific IL-2+IFNγ- and IL-2+IFNγ+ cells maintained significantly biased ratios of IFNγ+ and IFNγ- cells. IL-2+IFNγ- cells included both Tbetlo and Tbethi cells, and showed more mRNA expression differences with either of the IFNγ+ populations. To test whether IL-2+IFNγ-Tbetlo cells were Thpp cells (primed but uncommitted memory cells, predominant in responses to protein vaccines), influenza-specific IL-2+IFNγ- and IL-2+IFNγ+ T cells were sorted and cultured in Th1- or Th2-generating conditions. Both cell types yielded IFNγ-secreting cells in Th1 conditions, but only IL-2+IFNγ- cells were able to differentiate into IL-4-producing cells. Thus expression of IL-2 in the anti-influenza response may be regulated mainly by short term variability, whereas different T cell subsets, Th1 and Thpp, may contribute to variability in IFNγ expression. |
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| spelling | doaj.art-b37461f8b4924418ac25a0487e7adc962025-02-22T05:33:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0195e9598610.1371/journal.pone.0095986Cytokine diversity in the Th1-dominated human anti-influenza response caused by variable cytokine expression by Th1 cells, and a minor population of uncommitted IL-2+IFNγ- Thpp cells.Nan DengJason M WeaverTim R MosmannWithin overall Th1-like human memory T cell responses, individual T cells may express only some of the characteristic Th1 cytokines when reactivated. In the Th1-oriented memory response to influenza, we have tested the contributions of two potential mechanisms for this diversity: variable expression of cytokines by a uniform population during activation, or different stable subsets that consistently expressed subsets of the Th1 cytokine pattern. To test for short-term variability, in vitro-stimulated influenza-specific human memory CD4+ T cells were sorted according to IL-2 and IFNγ expression, cultured briefly in vitro, and cytokine patterns measured after restimulation. Cells that were initially IFNγ+ and either IL-2+ or IL-2- converged rapidly, containing similar proportions of IL-2-IFNγ+ and IL-2+IFNγ+ cells after culture and restimulation. Both phenotypes expressed Tbet, and similar patterns of mRNA. Thus variability of IL-2 expression in IFNγ+ cells appeared to be regulated more by short-term variability than by stable differentiated subsets. In contrast, heterogeneous expression of IFNγ in IL-2+ influenza-specific T cells appeared to be due partly to stable T cell subsets. After sorting, culture and restimulation, influenza-specific IL-2+IFNγ- and IL-2+IFNγ+ cells maintained significantly biased ratios of IFNγ+ and IFNγ- cells. IL-2+IFNγ- cells included both Tbetlo and Tbethi cells, and showed more mRNA expression differences with either of the IFNγ+ populations. To test whether IL-2+IFNγ-Tbetlo cells were Thpp cells (primed but uncommitted memory cells, predominant in responses to protein vaccines), influenza-specific IL-2+IFNγ- and IL-2+IFNγ+ T cells were sorted and cultured in Th1- or Th2-generating conditions. Both cell types yielded IFNγ-secreting cells in Th1 conditions, but only IL-2+IFNγ- cells were able to differentiate into IL-4-producing cells. Thus expression of IL-2 in the anti-influenza response may be regulated mainly by short term variability, whereas different T cell subsets, Th1 and Thpp, may contribute to variability in IFNγ expression.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0095986&type=printable |
| spellingShingle | Nan Deng Jason M Weaver Tim R Mosmann Cytokine diversity in the Th1-dominated human anti-influenza response caused by variable cytokine expression by Th1 cells, and a minor population of uncommitted IL-2+IFNγ- Thpp cells. PLoS ONE |
| title | Cytokine diversity in the Th1-dominated human anti-influenza response caused by variable cytokine expression by Th1 cells, and a minor population of uncommitted IL-2+IFNγ- Thpp cells. |
| title_full | Cytokine diversity in the Th1-dominated human anti-influenza response caused by variable cytokine expression by Th1 cells, and a minor population of uncommitted IL-2+IFNγ- Thpp cells. |
| title_fullStr | Cytokine diversity in the Th1-dominated human anti-influenza response caused by variable cytokine expression by Th1 cells, and a minor population of uncommitted IL-2+IFNγ- Thpp cells. |
| title_full_unstemmed | Cytokine diversity in the Th1-dominated human anti-influenza response caused by variable cytokine expression by Th1 cells, and a minor population of uncommitted IL-2+IFNγ- Thpp cells. |
| title_short | Cytokine diversity in the Th1-dominated human anti-influenza response caused by variable cytokine expression by Th1 cells, and a minor population of uncommitted IL-2+IFNγ- Thpp cells. |
| title_sort | cytokine diversity in the th1 dominated human anti influenza response caused by variable cytokine expression by th1 cells and a minor population of uncommitted il 2 ifnγ thpp cells |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0095986&type=printable |
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