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.
Wagner
Claudia S
CS
Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, S-141 86 Stockholm, Sweden. claudia.wagner@ki.se
Riise
Gerdt C
GC
Bergström
Tomas
T
Kärre
Klas
K
Carbone
Ennio
E
Berg
Louise
L
D000328:Adult; D000368:Aged; D024201:Bystander Effect / Q000276:immunology; D036022:Capsid Proteins / Q000096:biosynthesis / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000209:etiology / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism / Q000821:virology; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance; D007111:Immunity, Cellular; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D016040:Lung Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D036022:Capsid Proteins; D015395:Histocompatibility Antigens Class I; D011971:Receptors, Immunologic; C079750:VP23 protein, Human herpesvirus 1; C108073:leukocyte-associated immunoglobulin-like receptor 1