PMID- 17339449 OWN - NLM STAT- MEDLINE DCOM- 20070522 LR - 20190516 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 178 IP - 6 DP - 2007 Mar 15 TI - Increased expression of leukocyte Ig-like receptor-1 and activating role of UL18 in the response to cytomegalovirus infection. PG - 3536-43 AB - 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. FAU - Wagner, Claudia S AU - Wagner CS AD - Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, S-141 86 Stockholm, Sweden. claudia.wagner@ki.se FAU - Riise, Gerdt C AU - Riise GC FAU - Bergstrom, Tomas AU - Bergstrom T FAU - Karre, Klas AU - Karre K FAU - Carbone, Ennio AU - Carbone E FAU - Berg, Louise AU - Berg L LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Capsid Proteins) RN - 0 (Histocompatibility Antigens Class I) RN - 0 (Receptors, Immunologic) RN - 0 (VP23 protein, Human herpesvirus 1) RN - 0 (leukocyte-associated immunoglobulin-like receptor 1) SB - IM MH - Adult MH - Aged MH - Bystander Effect/immunology MH - Capsid Proteins/biosynthesis/*immunology MH - Cells, Cultured MH - Coculture Techniques MH - Cytomegalovirus/immunology MH - Cytomegalovirus Infections/etiology/*immunology/metabolism MH - Female MH - Fibroblasts/immunology/metabolism/virology MH - Histocompatibility Antigens Class I/immunology/metabolism MH - Humans MH - *Immune Tolerance MH - Immunity, Cellular MH - Killer Cells, Natural/immunology/metabolism MH - Lung Transplantation/*immunology MH - Male MH - Middle Aged MH - Receptors, Immunologic/biosynthesis/*immunology MH - T-Lymphocytes/*immunology/metabolism EDAT- 2007/03/07 09:00 MHDA- 2007/05/23 09:00 CRDT- 2007/03/07 09:00 PHST- 2007/03/07 09:00 [pubmed] PHST- 2007/05/23 09:00 [medline] PHST- 2007/03/07 09:00 [entrez] AID - 178/6/3536 [pii] AID - 10.4049/jimmunol.178.6.3536 [doi] PST - ppublish SO - J Immunol. 2007 Mar 15;178(6):3536-43. doi: 10.4049/jimmunol.178.6.3536.