Lipoic acid downmodulates CD4 from human T lymphocytes by dissociation of p56(Lck).
Lipoic acid is an antioxidant that suppresses and treats a model of multiple sclerosis, experimental autoimmune encephalomyelitis. We now demonstrate that treatment of human PBMC and T cell lines with LA downmodulated CD4 expression in a concentration-dependent manner. LA treatment of Con A stimulated PBMC specifically removed CD4 from the T-cell surface, but not CD3. Epitope masking by LA was excluded by using monoclonal antibodies targeting different domains of CD4. Incubation on ice inhibited CD4 removal following LA treatment, suggesting that endocytosis was involved in its downmodulation. LA is in a unique category of compounds that induce CD4 downmodulation by various mechanisms (e.g., gangliosides). We hypothesized that LA might induce dissociation of p56(Lck) from CD4, thus leading to its downmodulation. Immunoblot analyses demonstrated reduced co-precipitation of p56(Lck) from Jurkat T-cells following LA treatment and precipitation of CD4. This unique immunomodulatory effect of LA warrants further investigation.
Marracci
Gail H
GH
Portland Veterans Affairs Medical Center, R&D-65, 3710 SW US Veterans Hospital Road, Portland, OR 97239, USA. marracci@ohsu.edu
Marquardt
Whitney E
WE
Strehlow
Adrienne
A
McKeon
Gabriel P
GP
Gross
Jonathan
J
Buck
David C
DC
Kozell
Laura B
LB
Bourdette
Dennis N
DN
D000975:Antioxidants / Q000008:administration & dosage; D015704:CD4 Antigens / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D019169:Jurkat Cells; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism*; D011485:Protein Binding; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D008063:Thioctic Acid / Q000008:administration & dosage*
D000975:Antioxidants; D015704:CD4 Antigens; D008063:Thioctic Acid; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)