Thalidomide costimulates primary human T lymphocytes, preferentially inducing proliferation, cytokine production, and cytotoxic responses in the CD8+ subset.
The efficacy of thalidomide (alpha-phthalimido-glutarimide) therapy in leprosy patients with erythema nodosum leprosum is thought to be due to inhibition of tumor necrosis factor alpha. In other diseases reported to respond to thalidomide, the mechanism of action of the drug is unclear. We show that thalidomide is a potent costimulator of primary human T cells in vitro, synergizing with stimulation via the T cell receptor complex to increase interleukin 2-mediated T cell proliferation and interferon gamma production. The costimulatory effect is greater on the CD8+ than the CD4+ T cell subset. The drug also increases the primary CD8+ cytotoxic T cell response induced by allogeneic dendritic cells in the absence of CD4+ T cells. Therefore, human T cell costimulation can be achieved pharmacologically with thalidomide, and preferentially in the CD8+ T cell subset.
Haslett
P A
PA
The Rockefeller University, New York 10021-6399, USA. hasletp@rockvax.rockefeller.edu
Corral
L G
LG
Albert
M
M
Kaplan
G
G
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000938:Antigen-Presenting Cells / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D002455:Cell Division; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D003601:Cytotoxicity Tests, Immunologic; D003713:Dendritic Cells / Q000276:immunology; D004768:Enterotoxins / Q000276:immunology; D005404:Fixatives; D005976:Glutaral; D006801:Humans; D008934:Mitogens / Q000494:pharmacology*; D018089:Superantigens / Q000276:immunology; D013792:Thalidomide / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D016207:Cytokines; D004768:Enterotoxins; D005404:Fixatives; D008934:Mitogens; D018089:Superantigens; C026066:enterotoxin A, Staphylococcal; C031818:enterotoxin B, staphylococcal; D013792:Thalidomide; D005976:Glutaral