Expanded CD4+CD45RO+ phenotype and defective proliferative response in T lymphocytes from patients with Crohn's disease

doi:10.1053/gast.1996.v110.pm8612987

Gastroenterology

Volume 110, Issue 4, April 1996, Pages 1008-1019

https://doi.org/10.1053/gast.1996.v110.pm8612987 Get rights and content

Abstract

BACKGROUND & AIMS: An abnormal immune response may play a pathogenic role in Crohn's disease. The aim of this study was to determine the role of regulatory T cells in Crohn's disease. METHODS: T-cell phenotype and function were studied in blood lymphocytes from patients with Crohn's disease and a control group consisting of healthy donors and patients with ulcerative colitis. RESULTS: Flow cytometric studies showed a significant increase in the percentage of CD3+DR+ and CD4+CD45RO+ T cells in patients with Crohn's disease. T cells from patients with Crohn's disease and ulcerative colitis showed a defective proliferative response after stimulation with surface mitogenic ligands (phytohemagglutinin and anti-CD28 or anti-CD3 antibodies). Soluble interleukin-2 receptor alpha was augmented in the Crohn's disease and ulcerative colitis groups. In the Crohn's disease group, impairment of T-lymphocyte proliferation was normalized by exogenous interleukin 2, although endogenous interleukin-2 production and interleukin-2 receptor alpha expression were normal. CONCLUSIONS: An in vivo expansion of CD4+ T lymphocytes with memory phenotype and impaired T-cell proliferation that can be restored by pharmacological amounts of interleukin 2 was found in patients with Crohn's disease. There is a severe immunodisturbance in the T-cell compartment of patients with either clinically active or inactive Crohn's disease. (Gastroenterology 1996 Apr;110(4):1008-19)

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Citation Excerpt :
Triplicate cultures of 5 × 104 PBMCs per well were stimulated with 10 μg/mL of phytohemagglutinin (Difco Laboratories; Detroit, MI), 12.5 ng/mL soluble anti-CD3 antibodies (Orthomune; Orthodiagnostic System; Raritan, NJ), with or without 1.6 ng/mL anti-CD28 (Orthomune), or 100 IU/mL IL-2 in complete medium in 96-well, flat-bottomed microtiter plates (Nunc Corporation; Roskilde, Denmark). The amount of [methyl-3H]thymidine (Radiochemical Center; Amersham, UK) incorporated into the cultures was determined as previously described.24 PBMCs were incubated with combinations of fluorescein, phycoerythrin, and phycoerythrin-cyanine-5 conjugate-labeled monoclonal antibodies against CD3, CD4, CD8, CD14, CD19, CD28, CD45RA, and CD45RO (all by BD Biosciences; San Jose, CA) as previously described.16
Lymphocyte alterations have been associated with an increased prevalence of acute respiratory infections in COPD patients. AM3 is an oral immunomodulator that normalizes the defective functions of peripheral blood natural killer and phagocytic cells in COPD patients and improves their health-related quality of life.
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The study was a randomized, prospective, double-blind, placebo-controlled trial in a cohort of COPD patients. The results were also compared to those of nonsmoker and ex-smoker healthy control subjects.
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Peripheral blood mononuclear cell (PBMC) proliferation and production of interleukin (IL)-2, IL-4, IL-12p40, tumor necrosis factor-α, and interferon (IFN)-γ proteins in response to the T-cell polyclonal mitogens were assessed at baseline and at the end of treatment.
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