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 anti-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 HIV/TB were enhanced.
Bekker
L G
LG
Department of Medicine, University of Cape Town, South Africa.
Haslett
P
P
Maartens
G
G
Steyn
L
L
Kaplan
G
G
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000382:microbiology / Q000821:virology; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000328:Adult; D015992:Body Mass Index; D023201:CD40 Ligand; D016207:Cytokines / Q000097:blood; D005260:Female; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D008875:Middle Aged; D018121:Receptors, Cytokine / Q000097:blood; D013601:T-Lymphocytes / Q000276:immunology; D013792:Thalidomide / Q000494:pharmacology*; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology / Q000821:virology; D014779:Virus Replication
D000276:Adjuvants, Immunologic; D016207:Cytokines; D008562:Membrane Glycoproteins; D018121:Receptors, Cytokine; D023201:CD40 Ligand; D013792:Thalidomide