PMID- 1850961 OWN - NLM STAT- MEDLINE DCOM- 19910604 LR - 20181113 IS - 0002-9440 (Print) IS - 1525-2191 (Electronic) IS - 0002-9440 (Linking) VI - 138 IP - 5 DP - 1991 May TI - Induction of HLA-DR expression on thyroid follicular cells by cytomegalovirus infection in vitro. Evidence for a dual mechanism of induction. PG - 1209-23 AB - Cytomegalovirus (CMV) infection of primary cultures established from human thyroid nodular and normal (paranodular) tissues resulted in induction of human leukocyte antigen (HLA) DR expression on thyroid follicular cells (TFC), as detected by cell-surface immunofluorescence staining with monoclonal antibodies (MAb). Two distinct modalities of induction were observed. The first type occurred in cultures of normal tissue obtained from CMV-seropositive but not seronegative donors, was detected on 30% to 50% of the TFCs, even though the vast majority of these cells failed to show any morphologic or antigenic evidence of individual CMV infection, and was associated with production of gamma-interferon (gamma-IFN) in vitro. The induced molecules displayed the characteristic DR polypeptide profile on immunoprecipitation and electrophoretic analysis. These results demonstrate that CMV infection of normal thyroid cultures may induce DR expression on TFCs in the absence of pre-existing lymphoid infiltrates and suggest that the induction is the result of an in vitro response to CMV by previously sensitized immunocompetent cells present in these primary cultures. Such a response, associated with the release of gamma-IFN, would induce DR expression on neighboring uninfected cells. The second mode of induction occurred in all CMV-infected cultures, regardless of their tissue origin (nodular or normal) or the serologic status of the donors. Up to 50% of infected TFCs at a late stage of infection, having fully developed CMV antigen-positive intranuclear inclusions, also displayed the cell-surface DR-related determinant recognized by one of the four anti-DR MAbs used. This induction was restricted to TFCs, while CMV-infected fibroblastoid cells present in the monolayers were invariably negative. Induction by CMV of major histocompatibility class II antigens on human epithelial cells may have significant implications in the development of normal immune responses against local viral infection, the enhancement of alloimmune rejection of grafted organs, and the generation of organ-specific autoimmune responses. FAU - Khoury, E L AU - Khoury EL AD - Division of Oral Biology, University of California, San Francisco 94115. FAU - Pereira, L AU - Pereira L FAU - Greenspan, F S AU - Greenspan FS LA - eng GR - DK36164/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Am J Pathol JT - The American journal of pathology JID - 0370502 RN - 0 (Antibodies, Monoclonal) RN - 0 (HLA-DR Antigens) RN - 0 (Histocompatibility Antigens Class II) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Adult MH - Antibodies, Monoclonal/immunology MH - Cells, Cultured MH - Cytomegalovirus/isolation & purification/*physiology MH - Female MH - Fluorescent Antibody Technique MH - Gene Expression Regulation, Viral/*physiology MH - HLA-DR Antigens/genetics/immunology/*metabolism MH - Histocompatibility Antigens Class II/genetics/immunology/metabolism MH - Humans MH - Interferon-gamma/metabolism MH - Male MH - Middle Aged MH - Thyroid Gland/immunology/*metabolism/pathology PMC - PMC1886009 EDAT- 1991/05/01 00:00 MHDA- 1991/05/01 00:01 PMCR- 1991/11/01 CRDT- 1991/05/01 00:00 PHST- 1991/05/01 00:00 [pubmed] PHST- 1991/05/01 00:01 [medline] PHST- 1991/05/01 00:00 [entrez] PHST- 1991/11/01 00:00 [pmc-release] PST - ppublish SO - Am J Pathol. 1991 May;138(5):1209-23.