Porcine MHC classical class I genes are coordinately expressed in superantigen-activated mononuclear cells.
The expression of the major histocompatibility complex (MHC) classical class I genes is important for the adaptive immune response to target virus-infected cells and cancer cells. The up-regulation of the MHC is achieved by hormonal/cytokine signals including IFN-γ-inducible elements. The swine leukocyte antigen (SLA), the MHC class I region of pigs, consists of the duplicated classical class I genes, SLA-1, SLA-2 and SLA-3, but the molecular mechanisms involved in their up-regulation after T cell stimulation have not been fully elucidated. In order to better understand some of the putative regulatory mechanisms of SLA class I gene expression in activated T cells, we examined the coordinated expression of the SLA classical class I, IFN-γ and interferon regulatory factor-1 (IRF-1) genes in the peripheral blood mononuclear cells (PBMCs) of SLA homozygous Clawn miniature swine stimulated for 72 h with either IFN-γ or an enterotoxin produced by Staphylococcus aureus. This enterotoxin, toxic shock syndrome-1 (TSST-1), is known to act as a superantigen (sAG) to activate the T cells in various vertebrate species. We showed by using mAbs and flow cytometry that the CD4(+)CD25(+) cell number of swine PBMCs was also increased by TSST-1 and to a lesser degree by IFN-γ. Time course analyses of the expression of the IFN-γ, IRF-1 and the three classical class I genes, SLA-1, SLA-2, and SLA-3, in PBMCs by quantitative real-time PCR revealed a transitory response to TSST-1 or IFN-γ stimulation. The IFN-γ mRNA levels in the PBMCs were continuously up-regulated over the first 48 h by TSST-1 or IFN-γ. In contrast, SLA class I expression moderately increased at 24h and then decreased to a baseline level or less at 72 h of IFN-γ or TSST-1 stimulation. The three classical SLA class I genes showed similar expression kinetics, although SLA-3 mRNA level was consistently lower than those of SLA-1 and -2. The expression of IRF-1, a modulator of SLA expression, showed similar kinetics to those of the three classical SLA class I genes. The expression profiles detected by flow cytometry of the SLA molecules on the cell surface of PBMCs were maintained at a consistently high level during cell stimulation with either TSST-1 or IFN-γ, which was distinct from the kinetics of mRNA expression. These results showed that miniature swine SLA class I mRNA expression was effectively and equally up-regulated among the three loci and coordinately with IRF-1 gene expression after stimulation of T cell activation by sAG or IFN-γ.
Department of Immunology, Division of Basic Medical Science and Molecular Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1143, Japan.
Yoshie
Y
Kametani
Shino
S
Ohshima
Yuki F
YF
Kita
Shin
S
Shimada
Hiroshi
H
Kamiguchi
Takashi
T
Shiina
Hidetoshi
H
Inoko
Jerzy K
JK
Kulski
Asako
A
Ando
D000818:Animals; D001427:Bacterial Toxins / Q000494:pharmacology; D004768:Enterotoxins / Q000494:pharmacology; D005434:Flow Cytometry / Q000662:veterinary; D005786:Gene Expression Regulation / Q000276:immunology*; D005805:Genes, MHC Class I / Q000276:immunology / Q000502:physiology*; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D060888:Real-Time Polymerase Chain Reaction / Q000662:veterinary; D018089:Superantigens / Q000276:immunology* / Q000494:pharmacology; D013552:Swine / Q000235:genetics / Q000276:immunology; D013556:Swine, Miniature / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D001427:Bacterial Toxins; D004768:Enterotoxins; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal; C438668:swine leukocyte antigen; D007371:Interferon-gamma