The selective impact of transgenically expressed glucocorticoid receptor on T cells.
Glucocorticoids (GCs) strongly impact on different T cell subsets inducing generally immunosuppressive effects, whereas much less is known about the effect of GC on natural killer (NK) cells. The aims of this study were to investigate the effects of GC on T cell functions, including T cell-mediated anti-tumor immune response, and on NK cells. We have used lck-GR mice, which overexpress a transgenic rat GR in both T and NK cells. These mice were found to have decreased both CD4(+) and CD8(+) T cell populations in the periphery. In contrast, both NK and NKT cells were found in normal numbers in lck-GR mice. To identify genes and pathways affected by GR overexpression in our system in T cells, we have compared gene expression profiles in wild-type and lck-GR T cells. Among the genes upregulated in T cells from lck-GR mice, the microarray analysis has identified genes regulating expansion of regulatory T cells. The analysis of genes downregulated in lck-GR mice has identified genes and gene associated with the regulation of immune response. With regard to the effects on T cell functions in lck-GR mice, transgenic expression of GR had a suppressive effect on killer cell activity in vitro. In addition, lck-GR mice showed an increased tumor growth in murine tumor model in vivo, which may be a possible consequence of reduced T cell numbers and activity. We conclude that an increased expression of the GR strongly affects numbers and possibly functions of T cell subsets, but has little effect on NK cells.
Department of Biosciences and Nutrition, Karolinska Instutet , Novum, Huddinge , Sweden and.
Konstantin
K
Yakimchuk
Liying
L
Chen
Mohammad Sharif
MS
Hasni
Sam
S
Okret
Mikael
M
Jondal
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D015415:Biomarkers / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053450:Glucocorticoid-Induced TNFR-Related Protein / Q000235:genetics / Q000276:immunology; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018655:Lymphocyte Count; D016399:Lymphoma, T-Cell / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D055611:Natural Killer T-Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D061251:Primary Cell Culture; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics / Q000276:immunology; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000235:genetics* / Q000276:immunology; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
D015703:Antigens, CD; C488868:BTLA protein, mouse; D015415:Biomarkers; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053450:Glucocorticoid-Induced TNFR-Related Protein; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D011965:Receptors, Glucocorticoid; D011971:Receptors, Immunologic; C106544:Tnfrsf18 protein, mouse
Glucocorticoids; NK cells; T cells; microarray; tumor model