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

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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-γ secretion from IELs from day 7 infected mice, and was suppressed by treatment with anti-ICOS mAb. Additionally, IFN-γ 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-γ synthesis during infection.

Section snippets

Materials and methods

Mice and reagents. Adult female C57BL/6 mice, 6–8 weeks of age, were purchased from Harlan Spargue–Dawley; Indianapolis, IN. Mice were housed under specific pathogen-free conditions. Animals were used according to protocols approved by the Institutional Animal Care and Use Committee of the University of Texas Health Science Center at Houston. Cell culture medium consisted of RPMI-1640 supplemented with FCS (10% v/v) (Invitrogen; Carlsbad, CA), 100 U/ml penicillin–streptomycin, 2 mM l-glutamine,

During early phase of reovirus infection, actively proliferating IELs include both S7− and S7+ cells

Recent studies from our laboratory demonstrated the CD43 S7 isoform is differentially expressed on small intestinal IELs [13]. That property is also shown in the present study in Fig. 1A, which indicates that roughly equal proportions of IELs were S7− and S7+, and that each population included both TCRαβ and TCRγδ cells.

To understand the relationship between CD43 S7 expression during enteric virus infection, mice were infected with 107.5 pfu of reovirus 3 by oral gavage. Forty-eight hours prior

Discussion

Owing to their phenotypic and functional complexity [13], [31], [32], [33], [34], [35], [36], [37], [38], [39], understanding the contribution of intestinal IELs to the natural immune response during local antigen challenge has been difficult to fully assess. In a recent series of studies aimed at better understanding functional populations of IELs, we observed that murine IELs can be classified based on whether they express a CD43 glycoform recognized by mAb S7. Accordingly, S7+ IELs were

Acknowledgments

This work was supported by NIH Grant DK35566 and by Public Health Service Grant DK56338 to the Texas Gulf Coast Digestive Diseases Center.

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