NDLI: Transient CD86 expression on HCV specific CD8+ T cells in acute infection is linked to sufficient IL-2 signaling1

Content Provider	PubMed Central
Author	Radziewicz, Henry Ibegbu, Chris C. Hon, Huiming Bédard, Nathalie Bruneau, Julie Workowski, Kimberly A. Knechtle, Stuart J. Kirk, Allan D. Larsen, Christian P. Shoukry, Naglaa H. Arash, Grakoui
Abstract	Costimulatory signals via B7/CD28 family molecules (signal 2) are critical for effective adaptive CD8+ T cell immune responses. In addition to costimulatory signals, B7/CD28 family coinhibitory receptor/ligands have been identified that modulate immune responses. In acute HCV infection, PD-1, an inhibitory receptor in the CD28 family is highly expressed on virus specific CD8+ T cells, yet vigorous immune responses often still develop. We hypothesized that other costimulatory signals present during the acute phase of HCV infection would be important to counter this negative signaling. In this study, we report that (i) CD86 was highly expressed on HCV specific CD8+ T cells early in acute HCV infection and lost on transition to chronic HCV infection, (ii) Expression of CD86 was different from other “activation” markers since expression was delayed after in vitro TCR stimulation and required sufficient IL-2 signaling, and (iii) HCV specific CD8+ T cells in the liver of patients with chronic HCV infection were highly activated (CD69, CD38 and HLA-DR expression), but only a minority expressed CD86 or showed evidence of recent IL-2 signaling (low basal pSTAT5), despite persistent viremia. Our study identifies B7 ligand expression on HCV specific CD8+ T cells as a distinct marker of effective T cell stimulation with IL-2 signaling in acute HCV infection. Expression of costimulatory molecules such as CD86 early in HCV infection may be essential in overcoming inhibitory signals from the high-level of PD-1 expression also seen at this phase of infection.
Related Links	http://dx.doi.org/10.4049/jimmunol.0902994
Ending Page	2422
Page Count	13
Starting Page	2410
File Format	PDF
ISSN	15506606
e-ISSN	15506606
Journal	Journal of immunology (Baltimore, Md. : 1950)
Issue Number	5
Volume Number	184
Language	English
Publisher Date	2010-03-01
Access Restriction	Open
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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