Linomide inhibits programmed cell death of peripheral T cells in vivo.
Programmed cell death (PCD) is involved in the physiological regulation of lymphocyte turnover, as well in the antigen-driven selection of T and B cells. Here it is shown that the immunomodulator linomide (quinoline-3-carboxamide) inhibits the apoptotic decay of peripheral T lymphocytes in response to three different stimuli. First, linomide reduces the superantigen-mediated apoptosis and deletion of specific T lymphocytes of both the CD4+ and the CD8+ subsets without affecting other superantigen-triggered phenomena such as T cell expansion and anergy. Second, linomide abolishes the T lymphopenia and inhibits PCD of splenic CD4+ and CD8+ T cells induced by exogenous glucocorticoids. This effect is restricted to peripheral T lymphocytes and does not concern thymocytes. Finally, linomide abolishes the development of lymphopenia that follows infection with vaccinia virus, while reducing PCD of CD4+ and CD8+ peripheral T cells. The anti-apoptotic effect of linomide could account for its immunostimulatory properties and might be relevant to the treatment of immunodeficiencies associated with an increased apoptotic decay of T lymphocytes.
Gonzalo
J A
JA
Centro Nacional de Biotecnologia (CSIC), Universidad Autónoma de Madrid.
González-García
A
A
Kalland
T
T
Hedlung
G
G
Martínez
C
C
Kroemer
G
G
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D017635:Clonal Anergy / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D004768:Enterotoxins / Q000276:immunology; D005434:Flow Cytometry; D006912:Hydroxyquinolines / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016693:Receptors, Antigen, T-Cell, alpha-beta; D013154:Spleen / Q000166:cytology; D018089:Superantigens / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D014615:Vaccinia / Q000276:immunology
D000276:Adjuvants, Immunologic; D004768:Enterotoxins; D006912:Hydroxyquinolines; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens; C045282:roquinimex; C031818:enterotoxin B, staphylococcal; D003907:Dexamethasone