CD48 Controls T-Cell and Antigen-Presenting Cell Functions in Experimental Colitis

Ana C. Abadía-Molina, Honbing Ji, William Alvis Faubion, Aimée Julien, Yvette Latchman, Hideo Yagita, Arlene Sharpe, Atul K. Bhan, Cox Terhorst

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Background & Aims: The cell-surface receptor CD48 is a lipid-anchored protein expressed on all antigen-presenting cells and T cells. CD2 and 2B4 are known ligands for CD48, which themselves are expressed on the surface of hematopoietic cells. Here we examine the effect of CD48 in the development of chronic experimental colitis and how CD48 affects adaptive and innate immune functions. Methods: The role of CD48 in experimental colitis was first assessed by transferring CD4+CD45RBhi cells isolated from either wild-type or CD48-/- mice into either Rag-2-/- or CD48-/- × Rag-2-/- mice. Development of chronic colitis in these adoptively transferred mice was assessed by disease activity index, histology, and production of interferon-γ in mesenteric lymph nodes. Relevant functions of CD48-/-CD4+ T cells and CD48-/- macrophages were examined using in vitro assays. In a second set of experiments, the efficacy of anti-CD48 in prevention or treatment of chronic colitis was determined. Results: CD48-/-CD4+ cells induced colitis when transferred into Rag-2-/- mice, but not when introduced into CD48-/- × Rag-2-/- recipients. However, both recipient mouse strains developed colitis upon adoptive transfer of wild-type CD4+ cells. Consistent with a CD4+ T-cell defect was the observation that in vitro proliferation of CD48 -/-CD4+ T cells was impaired upon stimulation with CD48-/- macrophages. In vitro evidence for a modest macrophage functional defect was apparent because CD48-/- macrophages produced less tumor necrosis factor α and interleukin 12 than wild-type cells upon stimulation with lipopolysaccharide. Peritoneal macrophages also showed a defect in clearance of gram-negative bacteria in vitro. Treatment of the CD4 +CD45RBhi→Rag-2-/- mice or the wild-type BM→tgε26 mice with anti-CD48 (HM48-1) ameliorated development of colitis, even after its induction. Conclusions: Both CD48-dependent activation of macrophages and CD48-controlled activation of T cells contribute to maintaining the inflammatory response. Consequently, T cell-induced experimental colitis is ameliorated only when CD48 is absent from both T cells and antigen-presenting cells. Because anti-CD48 interferes with these processes, anti-human CD48 antibody treatment may represent a novel therapy for inflammatory bowel disease patients.

Original languageEnglish (US)
Pages (from-to)424-434
Number of pages11
JournalGastroenterology
Volume130
Issue number2
DOIs
StatePublished - Feb 2006
Externally publishedYes

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Viral Tumor Antigens
Antigen-Presenting Cells
Colitis
T-Lymphocytes
Macrophages
Lipid-Linked Proteins
Macrophage Activation
Adoptive Transfer
Peritoneal Macrophages
Cell Surface Receptors
Therapeutics
Interleukin-12
Gram-Negative Bacteria
Inflammatory Bowel Diseases
Interferons
Lipopolysaccharides
Histology
Tumor Necrosis Factor-alpha
Lymph Nodes
Ligands

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Abadía-Molina, A. C., Ji, H., Faubion, W. A., Julien, A., Latchman, Y., Yagita, H., ... Terhorst, C. (2006). CD48 Controls T-Cell and Antigen-Presenting Cell Functions in Experimental Colitis. Gastroenterology, 130(2), 424-434. https://doi.org/10.1053/j.gastro.2005.12.009

CD48 Controls T-Cell and Antigen-Presenting Cell Functions in Experimental Colitis. / Abadía-Molina, Ana C.; Ji, Honbing; Faubion, William Alvis; Julien, Aimée; Latchman, Yvette; Yagita, Hideo; Sharpe, Arlene; Bhan, Atul K.; Terhorst, Cox.

In: Gastroenterology, Vol. 130, No. 2, 02.2006, p. 424-434.

Research output: Contribution to journalArticle

Abadía-Molina, AC, Ji, H, Faubion, WA, Julien, A, Latchman, Y, Yagita, H, Sharpe, A, Bhan, AK & Terhorst, C 2006, 'CD48 Controls T-Cell and Antigen-Presenting Cell Functions in Experimental Colitis', Gastroenterology, vol. 130, no. 2, pp. 424-434. https://doi.org/10.1053/j.gastro.2005.12.009
Abadía-Molina, Ana C. ; Ji, Honbing ; Faubion, William Alvis ; Julien, Aimée ; Latchman, Yvette ; Yagita, Hideo ; Sharpe, Arlene ; Bhan, Atul K. ; Terhorst, Cox. / CD48 Controls T-Cell and Antigen-Presenting Cell Functions in Experimental Colitis. In: Gastroenterology. 2006 ; Vol. 130, No. 2. pp. 424-434.
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abstract = "Background & Aims: The cell-surface receptor CD48 is a lipid-anchored protein expressed on all antigen-presenting cells and T cells. CD2 and 2B4 are known ligands for CD48, which themselves are expressed on the surface of hematopoietic cells. Here we examine the effect of CD48 in the development of chronic experimental colitis and how CD48 affects adaptive and innate immune functions. Methods: The role of CD48 in experimental colitis was first assessed by transferring CD4+CD45RBhi cells isolated from either wild-type or CD48-/- mice into either Rag-2-/- or CD48-/- × Rag-2-/- mice. Development of chronic colitis in these adoptively transferred mice was assessed by disease activity index, histology, and production of interferon-γ in mesenteric lymph nodes. Relevant functions of CD48-/-CD4+ T cells and CD48-/- macrophages were examined using in vitro assays. In a second set of experiments, the efficacy of anti-CD48 in prevention or treatment of chronic colitis was determined. Results: CD48-/-CD4+ cells induced colitis when transferred into Rag-2-/- mice, but not when introduced into CD48-/- × Rag-2-/- recipients. However, both recipient mouse strains developed colitis upon adoptive transfer of wild-type CD4+ cells. Consistent with a CD4+ T-cell defect was the observation that in vitro proliferation of CD48 -/-CD4+ T cells was impaired upon stimulation with CD48-/- macrophages. In vitro evidence for a modest macrophage functional defect was apparent because CD48-/- macrophages produced less tumor necrosis factor α and interleukin 12 than wild-type cells upon stimulation with lipopolysaccharide. Peritoneal macrophages also showed a defect in clearance of gram-negative bacteria in vitro. Treatment of the CD4 +CD45RBhi→Rag-2-/- mice or the wild-type BM→tgε26 mice with anti-CD48 (HM48-1) ameliorated development of colitis, even after its induction. Conclusions: Both CD48-dependent activation of macrophages and CD48-controlled activation of T cells contribute to maintaining the inflammatory response. Consequently, T cell-induced experimental colitis is ameliorated only when CD48 is absent from both T cells and antigen-presenting cells. Because anti-CD48 interferes with these processes, anti-human CD48 antibody treatment may represent a novel therapy for inflammatory bowel disease patients.",
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AU - Ji, Honbing

AU - Faubion, William Alvis

AU - Julien, Aimée

AU - Latchman, Yvette

AU - Yagita, Hideo

AU - Sharpe, Arlene

AU - Bhan, Atul K.

AU - Terhorst, Cox

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