Correction of CD18-deficient lymphocytes by retrovirus-mediated gene transfer.
Leukocyte adhesion deficiency (LAD) is an inherited disorder of leukocyte function caused by derangements in CD18 expression. The genetic and functional abnormalities in a lymphocyte cell line from a patient with LAD have been corrected by retrovirus-mediated transduction of a functional CD18 gene. Lymphocytes from patients with LAD were exposed to CD18-expressing retrovirus and enriched for cells that express CD11a and CD18 (LFA-1) on the cell surface. Molecular and functional analyses of these cells revealed (i) one copy of proviral sequence per cell, (ii) viral-directed CD18 RNA that exceeded normal endogenous levels, (iii) normal quantities of CD11a and CD18 protein on the cell surface, and (iv) reconstitution of LFA-1-dependent adhesive function.
Wilson
J M
JM
Howard Hughes Medical Institute, Department of Internal Medicine, Ann Arbor, MI.
Ping
A J
AJ
Krauss
J C
JC
Mayo-Bond
L
L
Rogers
C E
CE
Anderson
D C
DC
Todd
R F
RF
D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics / Q000276:immunology; D018821:CD18 Antigens; D002449:Cell Aggregation; D002460:Cell Line; D002461:Cell Line, Transformed; D015870:Gene Expression; D015316:Genetic Therapy; D005822:Genetic Vectors; D004854:Herpesvirus 4, Human; D006801:Humans; D018370:Leukocyte-Adhesion Deficiency Syndrome; D016169:Lymphocyte Function-Associated Antigen-1; D008214:Lymphocytes / Q000276:immunology; D008562:Membrane Glycoproteins; D051379:Mice; D009693:Nucleic Acid Hybridization; D016028:Receptors, Leukocyte-Adhesion / Q000235:genetics / Q000276:immunology; D012190:Retroviridae / Q000235:genetics*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018821:CD18 Antigens; D016169:Lymphocyte Function-Associated Antigen-1; D008562:Membrane Glycoproteins; D016028:Receptors, Leukocyte-Adhesion; D013755:Tetradecanoylphorbol Acetate