Thoma S, Bonhagen K, Vestweber D, Hamann A, Reimann J
Department of Medical Microbiology, University of Ulm, Germany.
Eur J Immunol. 1998 Jun;28(6):1785-97. doi: 10.1002/(SICI)1521-4141(199806)28:06<1785::AID-IMMU1785>3.0.CO;2-Y.
Recruitment into the gut of CD4+ T cells and their activation in the colonic lamina propria (LP) are key events in the development of colitis in scid mice reconstituted with CD4+ T cells from immunocompetent, congenic donor mice. This study investigated the expression of cytokines and selectin-binding epitopes by CD4+ T cells repopulating different tissues of the adoptive scid host. Cells from the inflamed colonic LP of transplanted scid mice produced high amounts of IL-12, IFN-gamma and TNF-alpha but only low amounts IL-4 and IL-10. Intracellular cytokine staining confirmed the presence of large numbers of IFN-gamma- and TNF-alpha-producing effector CD4+ T cells in the colonic LP of scid mice with colitis but also in non-inflamed tissues [spleen (S), peritoneal cavity (PC) and mesenteric lymph nodes (mLN)] of the adoptive host. Cells from these tissues furthermore produced large amounts of IL-12. Ligands for endothelial selectins are involved in recruiting T cells into inflamed tissues. We have analyzed the expression of selectin-binding epitopes on CD4+ T cells repopulating different tissues of the adoptive scid host. We found that a large fraction of CD4+ T cells from inflamed colonic LP and from non-inflamed PC, mLN and S expressed high levels of P- and E-selectin-binding epitopes (P-Lhi) in transplanted scid mice, but not in congenic, immunocompetent control mice. Although P-Lhi CD4+ T cells were enriched in IFN-gamma-producing subsets from most (but not all) tissues, we also found large numbers of in vivo generated P-Llo CD4+ T cells producing pro-inflammatory cytokines. This was in contrast to in vitro generated Th1 CD4+ T blasts that were almost exclusively P-Lhi. In this mouse model, production of Th1-type pro-inflammatory cytokines and expression of surface epitopes binding endothelial selectins are hence strikingly up-regulated in CD4+ T cells residing in inflamed and non-inflamed tissues during the development of colitis.
将CD4+ T细胞募集到肠道并使其在结肠固有层（LP）中活化，是用来自免疫活性同基因供体小鼠的CD4+ T细胞重建的重症联合免疫缺陷（scid）小鼠发生结肠炎的关键事件。本研究调查了在过继scid宿主不同组织中重新填充的CD4+ T细胞的细胞因子表达和选择素结合表位。移植的scid小鼠炎症结肠LP中的细胞产生大量的IL-12、IFN-γ和TNF-α，但仅产生少量的IL-4和IL-10。细胞内细胞因子染色证实，患有结肠炎的scid小鼠的结肠LP中存在大量产生IFN-γ和TNF-α的效应CD4+ T细胞，在过继宿主的非炎症组织[脾脏（S）、腹腔（PC）和肠系膜淋巴结（mLN）]中也存在。来自这些组织的细胞还产生大量的IL-12。内皮选择素的配体参与将T细胞募集到炎症组织中。我们分析了在过继scid宿主不同组织中重新填充的CD4+ T细胞上选择素结合表位的表达。我们发现，在移植的scid小鼠中，来自炎症结肠LP以及非炎症PC、mLN和S的大部分CD4+ T细胞表达高水平的P-和E-选择素结合表位（P-Lhi），但在同基因免疫活性对照小鼠中则不然。尽管P-Lhi CD4+ T细胞在大多数（但不是所有）组织的产生IFN-γ的亚群中富集，但我们也发现大量体内产生的产生促炎细胞因子的P-Llo CD4+ T细胞。这与体外产生的Th1 CD4+ T母细胞几乎完全是P-Lhi形成对比。因此，在该小鼠模型中，在结肠炎发展过程中，驻留在炎症和非炎症组织中的CD4+ T细胞中，Th1型促炎细胞因子的产生和结合内皮选择素的表面表位的表达显著上调。
