Hierarchies in cytokine expression profiles for acute and resolving influenza virus-specific CD8+ T cell responses:: Correlation of cytokine profile and TCR avidity
Hierarchies in cytokine expression profiles for acute and resolving influenza virus-specific CD8+ T cell responses:: Correlation of cytokine profile and TCR avidity
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DOI：
10.4049/jimmunol.172.9.5553
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发表时间：
2004-05-01
影响因子：
4.4
通讯作者：
Doherty, PC
中科院分区：
文献类型：
--
作者：
La Gruta, NL;Turner, SJ;Doherty, PC
The development and resolution phases of influenza-specific CD8(+) T cell cytokine responses to epitopes derived from the viral nucleoprotein (D(b)PA(366)) and acid polymerase (D(b)PA(224)) were characterized in C57BL/6J mice for a range of anatomical compartments in the virus-infected lung and lymphoid tissue. Lymphocyte numbers were measured by IFN-gamma expression following stimulation with peptide, while the quality of the response was determined by the intensity of staining and the distribution of CD8(+) T cells producing TNF-alpha and IL-2. Both the levels of expression and the prevalence of TNF-alpha(+) and IL-2(+) cells reflected the likely Ag load, with clear differences being identified for populations from the alveolar space vs the lung parenchyma. Irrespective of the site or time of T cell recovery, IL-2(+) cells were consistently found to be a subset of the TNF-alpha(+) population which was, in turn, contained within the IFN-gamma(+) set. The capacity to produce IL-2 may thus be considered to reflect maximum functional differentiation. The hierarchy in cytokine expression throughout the acute phase of the primary and secondary response tended to be D(b)pA(224) > (DNP366)-N-b. Both elution studies with the cognate tetramers and experiments measuring CD8beta coreceptor dependence for peptide stimulation demonstrated the same D(b)PA(224) > (DNP366)-N-b profile for TCR avidity. Overall, the quality of any virus-specific CD8(+) T cell response appears variously determined by the avidity of the TCR-pMHC interaction, the duration and intensity of Ag stimulation characteristic of the particular tissue environment, and the availability of CD4(+) T help.
