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Research article2008Peer reviewedOpen access

Delayed contraction of the CD8(+) T cell response toward lymphocytic choriomeningitis virus infection in mice lacking serglycin

Grujic Miriana, Christensen Jan P., Sorensen Maria R., Abrink Magnus, Pejler Gunnar, Thomsen Allan R.

Abstract

We previously reported that the lack of serglycin proteoglycan affects secretory granule morphology and granzyme B (GrB) storage in in vitro generated CTLs. In this study, the role of serglycin during viral infection was studied by infecting wild-type (wt) mice and serglycin-deficient (SG(-/-)) mice with lymphocytic choriomeningitis virus (LCMV). Wt and SG(-/-) mice cleared 10(3) PFU of highly invasive LCMV with the same kinetics, and the CD8(+) T lymphocytes from wt and SG(-/-) animals did not differ in GrB, perforin, IFN-gamma, or TNF-alpha content. However, when a less invasive LCMV strain was used, SG(-/-) GrB(+) CD8(+) T cells contained similar to 30% less GrB than wt GrB(+) CD8(+) T cells. Interestingly, the contraction of the antiviral CD8(+) T cell response to highly invasive LCMV was markedly delayed in SG(-/-) mice, and a delayed contraction of the virus-specific CD8(+) T cell response was also seen after infection with vesicular stomatitis virus. BrdU labeling of cells in vivo revealed that the delayed contraction was associated with sustained proliferation of Ag-specific CD8(+) T cells in SG(-/-) mice. Moreover, wt LCMV-specific CD8(+) T cells from TCR318 transgenic mice expanded much more extensively in virus-infected SG(-/-) mice than in matched wt mice, indicating that the delayed contraction represents a T cell extrinsic phenomenon. In summary, the present report points to a novel, previously unrecognized role for serglycin proteoglycan in regulating the kinetics of antiviral CD8(+) T cell responses.

Published in

Journal of Immunology
2008, Volume: 181, number: 2, pages: 1043-1051 Publisher: American Association of Immunologists

        UKÄ Subject classification

        Animal and Dairy Science
        Veterinary Science

        Publication identifier

        DOI: https://doi.org/10.4049/jimmunol.181.2.1043

        Permanent link to this page (URI)

        https://res.slu.se/id/publ/20808