| 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. |
| Authors: |
Nan Deng; Jason M Weaver; Tim R Mosmann |
| Source: |
PLoS ONE, Vol 9, Iss 5, p e95986 (2014) |
| Publisher Information: |
Public Library of Science (PLoS) |
| Publication Year: |
2014 |
| Collection: |
Directory of Open Access Journals: DOAJ Articles |
| Subject Terms: |
Medicine; Science |
| 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 ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0095986&type=printable; https://doaj.org/toc/1932-6203; https://doaj.org/article/b37461f8b4924418ac25a0487e7adc96 |
| DOI: |
10.1371/journal.pone.0095986 |
| Availability: |
https://doi.org/10.1371/journal.pone.0095986; https://doaj.org/article/b37461f8b4924418ac25a0487e7adc96 |
| Accession Number: |
edsbas.946AF028 |
| Database: |
BASE |