Expression of the peripheral benzodiazepine receptor triggers thymocyte differentiation.
In the thymus, during T-cell differentiation, the expression of the peripheral benzodiazepine receptor (PBR) modulates. The protein level decreases between the double negative and double positive stages, and then increases when thymocytes become single positive. We addressed the role played by PBR in T-cell maturation. To this aim, we used Jurkat cells, which are immature T lymphocytes derived from an acute lymphoblastic leukemia. These cells are PBR negative and were stably transfected to achieve PBR levels similar to that in mature T cells. Using the DNA chip technology, we analyzed the PBR expression-dependent gene changes and evidenced that PBR-expressing cells exhibited more mature features than mock-transfected ones. A majority of the modulated genes encode proteins playing direct or indirect roles during the lymphocyte maturation process. In particular, PBR expression induced several differentiation markers (such as CD1, CD6), or key regulating elements (e.g., RAG1, RAG2, CD99, TCR). By contrast, some regulators of TCR signaling were reduced. PBR expression also affected the expression of critical apoptosis regulators: the proapoptotic lipocortin I, galectin-1, and galectin-9 were reduced while the antiapoptotic Bcl-2 was induced. Altogether our results supported the hypothesis that PBR controls T-cell maturation and suggested mechanisms through which PBR may regulate thymocyte-positive selection.
Immunology-Oncology Department, Sanofi-Synthelabo Recherche, 371 rue du Professeur Joseph Blayac, 34184 Montpellier cedex 04, France.
Pierrick
P
Rochard
Sylvaine
S
Galiegue
Norbert
N
Tinel
Annick
A
Peleraux
Annie
A
Bord
Omar
O
Jbilo
Pierre
P
Casellas
D017209:Apoptosis; D002454:Cell Differentiation; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D018613:Microscopy, Confocal; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D011963:Receptors, GABA-A / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology*
D011963:Receptors, GABA-A