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

• DOI: 10.1371/journal.pone.0095986
• Publication Date: 2014-05-01T20:47:07Z
• Authors: Nan Deng; Jason M. Weaver; Tim R. Mosmann
• Keywords: 0301 basic medicine; Science; Gene Expression Profiling; RNA Stability; Q; R; Gene Expression; T-Cell Antigen Receptor Specificity; Th1 Cells; 3. Good health; Interferon-gamma; 03 medical and health sciences; T-Lymphocyte Subsets; Influenza, Human; Medicine; Cluster Analysis; Cytokines; Humans; Interleukin-2; RNA, Messenger; Immunologic Memory; Cells, Cultured; Research Article

Within overall Th1-like human memory T cell responses, individual cells may express only some of the characteristic Th1 cytokines when reactivated. In Th1-oriented response to influenza, we have tested contributions two potential mechanisms for this diversity: variable expression by a uniform population during activation, or different stable subsets that consistently expressed cytokine pattern. To test short-term variability, in vitro-stimulated influenza-specific CD4+ were sorted according IL-2 and IFNγ expression, cultured briefly vitro, patterns measured after restimulation. Cells initially IFNγ+ either IL-2+ IL-2- converged rapidly, containing similar proportions IL-2-IFNγ+ IL-2+IFNγ+ culture Both phenotypes Tbet, mRNA. Thus variability appeared be regulated more than differentiated subsets. contrast, heterogeneous due partly After sorting, restimulation, IL-2+IFNγ- maintained significantly biased ratios IFNγ- cells. included both Tbetlo Tbethi cells, showed mRNA differences with populations. whether IL-2+IFNγ-Tbetlo Thpp (primed but uncommitted predominant responses protein vaccines), Th1- Th2-generating conditions. types yielded IFNγ-secreting conditions, able differentiate into IL-4-producing anti-influenza mainly short term whereas subsets, Thpp, contribute expression.