Role of T-cell-associated lymphocyte function-associated antigen-1 in the pathogenesis of experimental colitis
| Autor: | F. Stephen Laroux, Laura Gray, Dmitry V. Ostanin, Christopher G. Kevil, Kevin P. Pavlick, Kathryn L. Furr, Carla M. Brown, Matthew B. Grisham |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Colon
T-Lymphocytes medicine.medical_treatment T cell Lymphocyte Immunology chemical and pharmacologic phenomena Spleen Mice SCID Biology Monocytes Immunocompromised Host Mice medicine Animals Immunology and Allergy Mesenteric lymph nodes Mesentery CD11a Antigen IL-2 receptor Lymphocyte function-associated antigen 1 Colitis hemic and immune systems General Medicine Th1 Cells medicine.disease Molecular biology Lymphocyte Function-Associated Antigen-1 Mice Inbred C57BL Cytokine medicine.anatomical_structure Chronic Disease Cytokines Female Lymph Nodes Biomarkers |
| Zdroj: | International Immunology. 18:389-398 |
| ISSN: | 1460-2377 0953-8178 |
| DOI: | 10.1093/intimm/dxh378 |
| Popis: | The b2 integrin lymphocyte function-associated antigen-1 (LFA-1; CD11a/CD18) is important for lymphocyte trafficking and activation as well as recruitment to sites of tissue inflammation. The objective of this study was to assess the role of ‘T-cell-associated’ LFA-1 in the pathogenesis of chronic colitis in vivo. Transfer of CD4 1 CD25 � T cells isolated from wild-type (wt) mice into immunodeficient recipients [recombinase-activating gene-1-deficient (RAG-1 � /� )] produced moderate to severe colitis, whereas RAG-1 � /� mice injected with CD11a-deficient (CD11a � /� ; LFA-1 � /� ) donor T cells displayed minimal macroscopic and histological evidence of colitis. Surface expression of L-selectin, a4, a4b7 and chemokine receptor-7 were similar for wt and CD11a � /� donor T cells. Attenuated disease in the CD11a � /� ! RAG-1 � /� animals was associated with decreased numbers of CD4 1 T cells in the mesenteric lymph nodes (MLNs), spleen and intestinal lamina propria (LP). In addition, significant reductions in Th1 cytokines were observed following ex vivo stimulation of mononuclear cells obtained from the MLNs and colonic LP. Interestingly, mononuclear cells obtained from the spleens of CD11a � /� ! RAG-1 � /� exhibited enhanced pro-inflammatory cytokine production compared with splenocytes obtained from wt ! RAG-1 � /� colitic mice. Taken together, our data suggest that T-cell-associated CD11a (LFA-1) expression plays a dual role in the initiation of chronic gut inflammation by facilitating naive T-cell priming/activation and expansion within MLNs and by augmenting pro-inflammatory cytokine production following secondary stimulation by antigenpresenting cells in the colonic interstitium. |
| Databáze: | OpenAIRE |
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