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Title: Upregulation of ICOS on CD43+ CD4+ murine small intestinal intraepithelial lymphocytes during acute reovirus infection

Abstract

Murine intestinal intraepithelial lymphocytes (IELs) can be classified according to expression of a CD43 glycoform recognized by the S7 monoclonal antibody. In this study, we examined the response of S7+ and S7- IELs in mice during acute reovirus serotype 3 (Dearing strain) infection, which was confirmed by virus-specific real-time PCR. In vivo proliferation increased significantly for both S7- and S7+ IELs on day 4 post-infection as determined by BrdU incorporation; however, expression of the inducible costimulatory (ICOS) molecule, which peaked on day 7 post-infection, was upregulated on S7+ CD4+ T cells, most of which were CD4+8- IELs. In vitro ICOS stimulation by syngeneic peritoneal macrophages induced IFN-{gamma} secretion from IELs from day 7 infected mice, and was suppressed by treatment with anti-ICOS mAb. Additionally, IFN-{gamma} mRNA increased in CD4+ IELs on day 6 post-infection. These findings indicate that S7- and S7+ IELs are differentially mobilized during the immune response to reovirus infection; that the regulated expression of ICOS is associated with S7+ IELs; and that stimulation of IELs through ICOS enhances IFN-{gamma} synthesis during infection.

Authors:
 [1];  [1];  [2];  [3]
  1. Department of Diagnostic Sciences, Dental Branch, University of Texas Health Science Center at Houston, Houston, TX 77030 (United States)
  2. Research Center for Human Genetics, Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030 (United States)
  3. Department of Diagnostic Sciences, Dental Branch, University of Texas Health Science Center at Houston, Houston, TX 77030 (United States). E-mail: john.r.klein@uth.tmc.edu
Publication Date:
OSTI Identifier:
20798892
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 342; Journal Issue: 3; Other Information: DOI: 10.1016/j.bbrc.2006.02.031; PII: S0006-291X(06)00329-9; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BIOSYNTHESIS; CELL PROLIFERATION; IN VITRO; IN VIVO; LYMPHOCYTES; MACROPHAGES; MICE; MOLECULES; MONOCLONAL ANTIBODIES; POLYMERASE CHAIN REACTION; SECRETION; STIMULATION; VIRUSES

Citation Formats

Montufar-Solis, Dina, Garza, Tomas, Teng, B.-B., and Klein, John R. Upregulation of ICOS on CD43+ CD4+ murine small intestinal intraepithelial lymphocytes during acute reovirus infection. United States: N. p., 2006. Web. doi:10.1016/j.bbrc.2006.02.031.
Montufar-Solis, Dina, Garza, Tomas, Teng, B.-B., & Klein, John R. Upregulation of ICOS on CD43+ CD4+ murine small intestinal intraepithelial lymphocytes during acute reovirus infection. United States. doi:10.1016/j.bbrc.2006.02.031.
Montufar-Solis, Dina, Garza, Tomas, Teng, B.-B., and Klein, John R. Fri . "Upregulation of ICOS on CD43+ CD4+ murine small intestinal intraepithelial lymphocytes during acute reovirus infection". United States. doi:10.1016/j.bbrc.2006.02.031.
@article{osti_20798892,
title = {Upregulation of ICOS on CD43+ CD4+ murine small intestinal intraepithelial lymphocytes during acute reovirus infection},
author = {Montufar-Solis, Dina and Garza, Tomas and Teng, B.-B. and Klein, John R.},
abstractNote = {Murine intestinal intraepithelial lymphocytes (IELs) can be classified according to expression of a CD43 glycoform recognized by the S7 monoclonal antibody. In this study, we examined the response of S7+ and S7- IELs in mice during acute reovirus serotype 3 (Dearing strain) infection, which was confirmed by virus-specific real-time PCR. In vivo proliferation increased significantly for both S7- and S7+ IELs on day 4 post-infection as determined by BrdU incorporation; however, expression of the inducible costimulatory (ICOS) molecule, which peaked on day 7 post-infection, was upregulated on S7+ CD4+ T cells, most of which were CD4+8- IELs. In vitro ICOS stimulation by syngeneic peritoneal macrophages induced IFN-{gamma} secretion from IELs from day 7 infected mice, and was suppressed by treatment with anti-ICOS mAb. Additionally, IFN-{gamma} mRNA increased in CD4+ IELs on day 6 post-infection. These findings indicate that S7- and S7+ IELs are differentially mobilized during the immune response to reovirus infection; that the regulated expression of ICOS is associated with S7+ IELs; and that stimulation of IELs through ICOS enhances IFN-{gamma} synthesis during infection.},
doi = {10.1016/j.bbrc.2006.02.031},
journal = {Biochemical and Biophysical Research Communications},
number = 3,
volume = 342,
place = {United States},
year = {Fri Apr 14 00:00:00 EDT 2006},
month = {Fri Apr 14 00:00:00 EDT 2006}
}
  • Highlights: •Small intestinal epithelial cells (sIECs). •sIECs are able to induce antigen specific proliferation of CD4{sup +} IELs. •sIECs induce markedly enhanced IFN-γ secretion by CD4{sup +} IELs. •Induction of enhanced IFN-γ secretion by sIECs is uniquely observed in CD4{sup +} IELs. -- Abstract: Small intestinal epithelial cells (sIECs) express major histocompatibility complex class II molecules even in a normal condition, and are known to function as antigen presenting cells (APCs) at least in vitro. These findings raised the possibility that sIECs play an important role in inducing immune responses against luminal antigens, especially those of intestinal intraepithelial lymphocytes (IELs)more » and lamina propria lymphocytes (LPLs). We herein showed that antigenic stimulation with sIECs induced markedly greater secretion of interferon-gamma (IFN-γ) by CD4{sup +} IELs, but not interleukin (IL)-4, IL-10 and IL-17 although the proliferative response was prominently lower than that with T cell-depleted splenic APCs. In contrast, no enhanced IFN-γ secretion by CD4{sup +} LPLs and primed splenic CD4{sup +} T cells was observed when stimulated with sIECs. Taken together, these results suggest that sIECs uniquely activate CD4{sup +} IELs and induce remarkable IFN-γ secretion upon antigenic stimulation in vivo.« less
  • Intestinal intraepithelial lymphocytes (IEL) that reside at basolateral site regulate the proliferation and differentiation of epithelial cells (EC) for providing a first line of host defense in intestine. However, it remains unknown how IEL interact and communicate with EC. Here, we show that IEL express junctional molecules like EC. We identified mRNA expression of the junctional molecules in IEL such as zonula occludens (ZO)-1, occludin and junctional adhesion molecule (JAM) (tight junction), {beta}-catenin and E-cadherin (adherens junction), and connexin26 (gap junction). IEL constitutively expressed occludin and E-cadherin at protein level, while other T cells in the thymus, spleen, liver, mesentericmore » lymph node, and Peyer's patches did not. {gamma}{delta} IEL showed higher level of these expressions than {alpha}{beta} IEL. The expression of occludin was augmented by anti-CD3 Ab stimulation. These results suggest the possibility of a novel role of IEL concerning epithelial barrier and communication between IEL and EC.« less
  • Highly purified preparations of intraepithelial leukocytes (IEL) were obtained from the small intestinal mucosa. Because approximately 80% of IEL expressed the Lyt-2 antigen usually associated with cytotoxic/suppressor T lymphocytes, the authors wished to determined if precursors for cytotoxic T cells were present in this population. In order to generate cytotoxic cells, IEL and spleen cells from CBA/J mice (H-2/sup k/) were co-cultured with irradiated allogeneic spleen cells (H-2/sup d/ or H-2/sup b/) in a one-way mixed leukocyte reaction (MLR). Four to six days later, the culture cells were assayed against /sup 51/Cr-labeled H-2/sup d/ or H-2/sup b/ tumor of Conmore » A-stimulated lymphoblast target cells, and the specificity of alloantigen-stimulated IEL and spleen cells was compared. The cytotoxic cells derived from both tissues displayed antigen-specific lysis of the allogeneic targets. Treatment of effector cells, generated from intraepithelial or splenic precursors, with monoclonal antibodies against Thy-1.2, Lyt-1.1, or Lyt-2.1 antigens plus complement, decreased cytotoxicity 85 to 100%, event though only 20 to 50% of the cells were lysed. The alloantigen specificity and surface antigen phenotype of the cultured IEL cells were identical to those of spleen cells and allowed them to conclude that IEL contained a cytotoxic T lymphocyte precursor (CTLp).« less
  • The kinetics of postnatal intestinal colonization by T cells carrying gamma delta and alpha beta T-cell antigen receptors were studied in nude and normal mice by flow cytometry and immunohistology. Furthermore, gamma delta and alpha beta T-cell development was analyzed in lethally irradiated mice that were reconstituted by fetal liver precursors with or without a thymus. Our results establish that a major subpopulation of gamma delta intestinal intraepithelial lymphocytes is produced from uncommitted precursors at extrathymic sites. This work further shows that a small pool of T cells carrying alpha beta T-cell receptors can also differentiate extrathymically from CD3- fetalmore » liver precursors but with rates of production and peripheral expansion much reduced as compared with those observed in thymus-bearing animals.« less
  • The authors used virus assay and in situ hybridization with a cloned fragment of the murine cytomegalovirus (MCMV) genome to study MCMV infection of circulating leukocytes harvested from 3-week-old BALB/c, C57BL/6, and C3H mice infected with MCMV intraperitoneally. Infectious virus or MCMV DNA was detected in leukocytes on days 1 through 21 of infection in BALB/c mice and on days 3 through 7 in C57BL/6 mice. On days 5 and 7, MCMV DNA or infectious virus was detected in the leukocytes of 17 (94%) of 18 BALB/c mice and 10 (59%) of 17 C57BL/6 mice. In both strains infection peakedmore » on days 5 and 7, when as many as 0.01 to 0.1% of the circulating leukocytes contained MCMV DNA. In C3H mice, however, infectious virus was rarely recovered from leukocyte fractions and MCMV DNA was detected in the circulating leukocytes of only one animal. Circulating leukocytes may have an important role in the dissemination of CMV infections in susceptible hosts.« less