Campbell J Darren, Stinson Monique J, Simons F Estelle R, HayGlass Kent T
Departments of Immunology, Basic Medical Sciences Building, 730 William Avenue, Winnipeg, Manitoba R3E 0W3, Canada.
Int Immunol. 2002 Nov;14(11):1255-62. doi: 10.1093/intimm/dxf098.
T(h)1- and T(h)2-polarized human T cell clones display distinct patterns of chemokine receptor expression and selective chemokine responsiveness in vitro. We hypothesized that natural exposure to environmental grass pollen would induce differential systemic chemokine and chemokine receptor expression patterns in individuals with allergic rhinitis compared to healthy controls with type 2- and type 1-dominated responses to allergen respectively. To this end, we compared chemokine receptor expression on peripheral blood T cells directly ex vivo and plasma chemokine levels between these two groups of study participants prior to and during the grass pollen season. T(h)1-associated CXC chemokine receptor (CXCR) 3 was strongly expressed on >50% CD4(+)/CD45RO(+) cells of all subjects. When examined longitudinally, CXCR3 expression increased over the grass pollen season (P < 0.0001), solely in non-allergic subjects. In contrast, for both allergic and non-allergic subjects, CC chemokine receptor (CCR) 5 (T(h)1-associated) and CCR3 (T(h)2-associated) were weakly expressed on <10% of CD4(+)/CD45RO(+) cells both prior to and during the grass pollen season. Type 1 chemokines CXC chemokine ligand (CXCL) 9 and CXCL10 (monokine induced by IFN-gamma and IFN-gamma-inducible protein of 10 kDa: CXCR3 ligands), and type 2 chemokines CC chemokine ligand (CCL) 11 (eotaxin: CCR3 ligand), CCL17 (thymus and activation-regulated chemokine: CCR4 ligand) and CCL22 (monocyte-derived chemokine: CCR4 ligand) were readily detectable in the plasma of most participants. Systemic CXCL9 levels decreased from pre- to grass pollen season in allergics (P < 0.05), whereas CCL17 decreased in non-allergics (P < 0.05) over the same period. Taken together, these longitudinal data suggest a systemic shift to more intensely type 1-dominated responses in non-allergic individuals and, conversely, to more type 2-dominated responses in allergic individuals upon natural re-exposure to grass pollen.
T(h)1和T(h)2极化的人T细胞克隆在体外表现出不同的趋化因子受体表达模式和选择性趋化因子反应性。我们假设，与分别对过敏原呈2型和1型主导反应的健康对照相比，自然暴露于环境草花粉会在过敏性鼻炎个体中诱导不同的全身趋化因子和趋化因子受体表达模式。为此，我们比较了这两组研究参与者在草花粉季节之前和期间外周血T细胞直接离体时趋化因子受体的表达以及血浆趋化因子水平。所有受试者中，>50%的CD4(+)/CD45RO(+)细胞上强烈表达与T(h)1相关的CXC趋化因子受体（CXCR）3。纵向观察时，仅在非过敏受试者中，CXCR3表达在草花粉季节期间增加（P < 0.0001）。相反，对于过敏和非过敏受试者，在草花粉季节之前和期间，CC趋化因子受体（CCR）5（与T(h)1相关）和CCR3（与T(h)2相关）在<10%的CD4(+)/CD45RO(+)细胞上弱表达。1型趋化因子CXC趋化因子配体（CXCL）9和CXCL10（由IFN-γ诱导的单核因子和10 kDa的IFN-γ诱导蛋白：CXCR3配体），以及2型趋化因子CC趋化因子配体（CCL）11（嗜酸性粒细胞趋化因子：CCR3配体）CCL17（胸腺和活化调节趋化因子：CCR4配体）和CCL22（单核细胞衍生趋化因子：CCR4配体）在大多数参与者的血浆中易于检测到。过敏者血浆中全身CXCL9水平从草花粉季节前到季节期间下降（P < 0.05），而同期非过敏者中CCL17下降（P < 0.05）。综上所述，这些纵向数据表明，在自然再次暴露于草花粉时，非过敏个体全身向更强烈的1型主导反应转变，相反，过敏个体则向更强烈的2型主导反应转变。
