CD4(+)CD8(+)TCR(low) thymocytes express low levels of glucocorticoid receptors while being sensitive to glucocorticoid-induced apoptosis.
While signaling by either the TCR or glucocorticoid receptor (GR) can induce apoptosis in thymocytes, recent studies have shown that combining these signals results in survival of CD4(+)CD8(+) thymocytes. Although glucocorticoids (GC) in this way may directly affect T cell selection, no data are available addressing GR expression in thymocyte subsets and in individual cells within subsets. We studied GR expression by combining immunofluorescence cell surface staining for CD4, CD8 and TCR with intracellular staining of GR in four-color cytometry. Significant differences of GR expression were observed in various thymocyte subsets, although a homogeneous distribution of GR expression in individual thymocyte subsets emerged. The highest GR expression was found in CD4(-)CD8(-)TCR(-) thymocytes, and decreased during development via the CD4(-)CD8(+)TCR(-) subpopulation into the CD4(+)CD8(+)TCR(low) subset. Interestingly, the latter population, although expressing less than half the GR density of CD4(-)CD8(-)TCR(-) cells, is the most sensitive subset to GC-induced apoptosis. Up-regulation of TCR expression by the CD4(+)CD8(+)TCR(low) subset to CD4(+)CD8(+)TCR(high) cells was accompanied by a parallel increase in GR expression. The latter finding and the presence of a homogeneous distribution of GR in each thymocyte subset provides an experimental basis for the concept that GR can antagonize TCR-mediated signals at a constant rate relative to TCR expression.
Wiegers
G J
GJ
Institute for General and Experimental Pathology, Medical School, University of Innsbruck, Austria.
Knoflach
M
M
Böck
G
G
Niederegger
H
H
Dietrich
H
H
Falus
A
A
Boyd
R
R
Wick
G
G
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015704:CD4 Antigens / Q000378:metabolism*; D016827:CD8 Antigens / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D008024:Ligands; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
D015704:CD4 Antigens; D016827:CD8 Antigens; D005938:Glucocorticoids; D008024:Ligands; D019253:Proto-Oncogene Proteins c-bcl-2; D011948:Receptors, Antigen, T-Cell; D011965:Receptors, Glucocorticoid