Expression of selectin-binding epitopes and cytokines by CD4+ T cells repopulating scid mice with colitis

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • Colitis / immunology*
  • Colitis / pathology
  • Cytokines / biosynthesis*
  • Endothelium, Lymphatic / immunology
  • Epitopes, T-Lymphocyte / biosynthesis*
  • Female
  • Immunologic Memory
  • Interferon-gamma / immunology
  • Ligands
  • Lymphocyte Activation
  • Lymphoid Tissue / immunology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, SCID
  • P-Selectin / immunology*
  • Th1 Cells / immunology
  • Th2 Cells / immunology
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Up-Regulation


  • Cytokines
  • Epitopes, T-Lymphocyte
  • Ligands
  • P-Selectin
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma