Thalidomide can costimulate or suppress CD4+ cells' ability to incorporate [H3]-thymidine--dependence on the primary stimulant.
Thalidomide is a drug that can enhance mitogen- and antigen-stimulated cells' ability to synthesize IL-2. To assess if thalidomide could concomitantly enhance the synthesis of IFN-gamma and incorporation of [H3]-thymidine, peripheral blood mononuclear cells (PBMC) were incubated in the presence or absence of thalidomide and staphylococcal enterotoxin A (SEA), anti-CD3, Con-A or PHA. After 18 h, the cultures were sampled for IL-2. At the termination of the 3-day cultures, they were assayed for IFN-gamma and incorporation of [H3]-thymidine. Regardless of the mitogen used to stimulate the PBMC, the thalidomide-treated PBMC produced more IL-2 than controls. Thalidomide enhanced IFN-gamma synthesis in the Con-A and anti-CD3-stimulated PBMC. It suppressed the ability of SEA and PHA-stimulated PBMC to incorporate [H3]-thymidine, whereas it enhanced incorporation of [H3]-thymidine in PBMCs stimulated with anti-CD3. When the PBMC were enriched for CD4+ or CD8+ cells, the SEA- and anti-CD3-stimulated CD4+ cells responded far better than the CD8+ cells in the synthesis of IL-2 and incorporation of [H3]-thymidine. In the thalidomide-treated SEA-stimulated CD4+ and CD8+ cells, thalidomide acted as a costimulant to enhance the synthesis of IL-2. In the anti-CD3-stimulated thalidomide-treated cultures of PBMC enriched for CD4+ cells, thalidomide acted as a costimulant to enhance the incorporation [H3]-thymidine. Thalidomide cooperated with all of the mitogens to enhance T-cell synthesis of IL-2. However, depending on the stimulant, thalidomide could suppress or enhance PBMC incorporation of [H3]-thymidine. The SEA-stimulated cells targeted by thalidomide to suppress incorporation of [H3]-thymidine were CD4+. CD4+ cells stimulated with anti-CD3 were enhanced by thalidomide in their ability to synthesize IL-2 and to incorporate [H3]-thymidine. Increased production of IL-2 by activated T cells may be a mechanism through which thalidomide exerts its immunomodulatory effects.
D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D013792:Thalidomide / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism*; D014316:Tritium / Q000378:metabolism
D016207:Cytokines; D014316:Tritium; D013792:Thalidomide; D013936:Thymidine