Steroid receptor-mediated modulation of CD4+CD62L+ cell homing. Implications for drug abusers.
Naive human T cells home to peripheral lymph nodes via the leukocyte endothelial cell adhesion molecule-1 (LECAM-1, l-selectin, CD62L, Leu8 antigen) they express. We enriched populations of CD4+CD62L+ cells (attachment of Leu8+ T cells to flasks coated with anti-mouse IgG (AIS); Leu8+ T cells, 82.3% pure (+/- 2.3%), enriched for CD4+ cells by incubation over flasks coated with anti-CD4 antibody--this 3-4-day procedure yields an 88 +/- 1.4% recovery. Cells were treated with dexamethasone in vitro for 24-48 h, and monitored by flow cytometry. We found severe toxicity by this steroid at high concentration (10(-6) M: 35% decrease in CD62L+ T cells, 22% drop specifically in CD4+CD62L+ cells), suggesting the onset of receptor-mediated apoptotic events. The toxicity was dose dependent (5% and 7% drop in CD62L+ T and CD4+CD62L+ cells, respectively, at 10(-9) M, the concentration found in plasma 10 h following the administration of 1 mg dexamethasone). One mg of dexamethasone given to normal subjects leads to a 15-20% decrease in circulating CD4+CD62L+ cells at 10 h. This tends to be correlated with a drop in the number of glucocorticoid cytosolic receptors. Thus, steroids seem to modulate CD4+CD62L+ cell homing by means of receptor-mediated mechanisms.
Chiappelli
F
F
Laboratory of Human Oral and Molecular Immunology, Diagnostic Sciences, School of Dentistry, Department of Neurobiology, School of Medicine, Brain & Dental Research Institutes, University of California, Los Angeles 90024-1668.
Manfrini
E
E
Gwirtsman
H
H
Garcia
C
C
Pham
L
L
Lee
P
P
Frost
P
P
D000328:Adult; D015703:Antigens, CD / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000502:physiology; D003907:Dexamethasone / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008198:Lymph Nodes / Q000276:immunology*; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins / Q000097:blood*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D003907:Dexamethasone; D006854:Hydrocortisone