Hydroxyurea exerts an anti-proliferative effect on T cells but has no direct impact on cellular activation.
Hydroxyurea (HU) is a cytostatic drug which has been used as an anti-HIV agent due mainly to its synergistic activity when combined with certain anti-retrovirals. In addition, HU might have a beneficial effect on parameters involved in the pathogenesis of HIV infection, such as immune activation. To test this hypothesis, the effect of HU on T cell proliferation and T cell activation, as well as the potential association between these two phenomena, were examined in an in vitro model. HU exerted a dose-dependent anti-proliferative effect on T cells, and modulated the expression of different activation markers. In cells exposed to HU, expression of CD25 and CD38 diminished in a dose-dependent manner, whereas expression of CD69 increased. However, when the expression of these markers was examined separately on proliferating and non-proliferating lymphocytes, HU did not exert any significant effect. Thus, the effect of HU on T cell activation is not direct and seems to be mediated through its effect on T cell proliferation.
Benito
J M
JM
Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain. jbenitol@hotmail.com
López
M
M
Lozano
S
S
Ballesteros
C
C
González-Lahoz
J
J
Soriano
V
V
D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D019380:Anti-HIV Agents / Q000494:pharmacology*; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D000099192:CD69 Antigens
D051997:ADP-ribosyl Cyclase 1; D019380:Anti-HIV Agents; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D006918:Hydroxyurea; D053645:Interleukin-2 Receptor alpha Subunit; D037181:Lectins, C-Type; D000099192:CD69 Antigens