Thalidomide-induced antigen-specific immune stimulation in patients with human immunodeficiency virus type 1 and tuberculosis

Thalidomide, which inhibits monocyte tumor necrosis factor (TNF)-alpha production and costimulates T cells, was tested for immune modulation in patients with human immunodeficiency virus (HIV) infection and tuberculosis (TB) in a placebo-controlled study. Thalidomide therapy resulted in increased levels of plasma interleukin (IL)-2 receptor, soluble CD8, interferon-gamma, and IL-12, indicating immune stimulation. TNF-alpha levels were not reduced. Thalidomide treatment increased CD4(+) and CD8(+) T cell counts and lymphocyte proliferation to purified protein derivative. Immune stimulation was not associated with an increase in plasma HIV levels. In vivo, a thalidomide dose-dependent costimulatory effect on T cell proliferation and HIV replication was observed after stimulation with antigens or antf-CD3, respectively Thalidomide-induced increased viral replication in CD4(+) T cells was abrogated by adding back autologous CD8(+) T cells. Thus, in the presence of thalidomide, antigen-specific immune responses in vitro and in patients with HTV/TB were enhanced.