Increased expression of leukocyte Ig-like receptor-1 and activating role of UL18 in the response to cytomegalovirus infection

NK and T cells are important for combating CMV infection. Some NK and T cells express leukocyte Ig-like receptor-1 (LIR-1), an inhibitory receptor recognizing MHC class I and the CMV-encoded homolog UL18. We previously demonstrated an early increase in LIR-1-expressing blood lymphocytes in lung-transplanted patients later developing CMV disease. We now show that NK and T cells account for the observed LIR-1 augmentation. Coincubation of PBMC from CMV-seropositive donors with virus-infected lung fibroblasts led to a T cell-dependent secretion of IFN-gamma, produced mainly by LIR-1(+) T cells and by NK cells. Cytokine production during coculture with fibroblasts infected with virus containing the UL18 gene was augmented compared with the UL18 deletion virus, suggesting a stimulatory role for UL18. However, purified UL18Fc proteins inhibited IFN-gamma production of LIR-1(+) T cells. We propose that cytokine production in the transplant induces NK and T cells to express LIR-1, which may predispose to CMV disease by MHC/LIR-1-mediated suppression. Although the UL18/LIR-1 interaction could inhibit T cell responses, this unlikely plays a role in response to infected cells. Instead, our data point to an activating role for viral UL18 during infection, where indirect intracellular effects cannot be excluded.

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Lungmedicin och allergi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Respiratory Medicine and Allergy hsv//eng
Adult
Aged
Bystander Effect/immunology
Capsid Proteins/biosynthesis/*immunology
Cells
Cultured
Coculture Techniques
Cytomegalovirus/immunology
Cytomegalovirus Infections/etiology/*immunology/metabolism
Female
Fibroblasts/immunology/metabolism/virology
Histocompatibility Antigens Class I/immunology/metabolism
Humans
*Immune Tolerance
Immunity
Cellular
Killer Cells
Natural/immunology/metabolism
Lung Transplantation/*immunology
Male
Middle Aged
Receptors
Immunologic/biosynthesis/*immunology
T-Lymphocytes/*immunology/metabolism

Riise, Gerdt C.,1956Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Institute of Medicine, Department of Internal Medicine(Swepub:gu)xriige (author)
Bergström, Tomas,1950Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Institute of Biomedicine, Department of Infectious Medicine(Swepub:gu)xberto (author)
Kärre, K.Karolinska Institutet (author)
Carbone, E.Karolinska Institutet (author)
Berg, L.Karolinska Institutet (author)
Göteborgs universitetInstitutionen för medicin, avdelningen för invärtesmedicin (creator_code:org_t)

In:J Immunol: The American Association of Immunologists178:6, s. 3536-430022-17671550-6606

By the author/editor: Wagner, C. S.; Riise, Gerdt C., ...; Bergström, Tomas ...; Kärre, K.; Carbone, E.; Berg, L.

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Respiratory Medi ...

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