Delayed contraction of the CD8+ T cell response toward lymphocytic choriomeningitis virus infection in mice lacking serglycin.
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 approximately 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.
Grujic
Mirjana
M
University of Copenhagen, Institute of International Health, Immunology and Microbiology, Copenhagen, Denmark.
Christensen
Jan P
JP
Sørensen
Maria R
MR
Abrink
Magnus
M
Pejler
Gunnar
G
Thomsen
Allan R
AR
D000818:Animals; D001117:Arenaviridae Infections / Q000276:immunology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D053804:Granzymes / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000821:virology; D008213:Lymphocyte Activation; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D054353:Perforin / Q000378:metabolism; D011509:Proteoglycans / Q000235:genetics / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism; D054243:Vesicular Stomatitis / Q000276:immunology* / Q000821:virology; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000502:physiology*; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology
D011509:Proteoglycans; D014409:Tumor Necrosis Factor-alpha; D033921:Vesicular Transport Proteins; C075430:serglycin; D054353:Perforin; D007371:Interferon-gamma; D053804:Granzymes; C509214:Gzmb protein, mouse