Transforming growth factor beta and noncytopathic mechanisms of immunodeficiency in human immunodeficiency virus infection.
This study examines the contribution of transforming growth factor beta (TGF beta), one of the most potent endogenous immunosuppressive factors, to the development of immunodeficiency in human immunodeficiency virus (HIV) infection. Increased titers of TGF beta were found in supernatants of peripheral blood mononuclear cells (PBMCs) from HIV-infected donors as compared to uninfected controls (P less than 0.001). This correlated closely with defective responses of CD4+ lymphocytes to the recall antigens tuberculin purified protein derivative or tetanus toxoid. The addition of TGF beta-neutralizing antibody to PBMCs partially restored these defective T-cell responses. Furthermore, purified TGF beta or HIV+ PBMC culture supernatants preferentially inhibited proliferation of CD4+ lymphocytes as compared to CD8+ cells. The increased expression of the TGF beta protein was associated with increased TGF beta mRNA as determined by a polymerase chain reaction assay. This increase in TGF beta protein and mRNA was due to a selective upregulation of the TGF beta 1 isoform. These results indicate that overexpression of TGF beta 1 occurs in HIV-infected individuals and that this cytokine can contribute to impaired immune functions and to depletion of CD4+ T lymphocytes.
Kekow
J
J
Department of Molecular and Experimental Medicine, Research Institute of Scripps Clinic, La Jolla, CA 92037.
Wachsman
W
W
McCutchan
J A
JA
Cronin
M
M
Carson
D A
DA
Lotz
M
M
D000163:Acquired Immunodeficiency Syndrome / Q000097:blood* / Q000276:immunology; D001483:Base Sequence; D015704:CD4 Antigens / Q000032:analysis; D002455:Cell Division; D002478:Cells, Cultured; D015658:HIV Infections / Q000097:blood* / Q000276:immunology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000473:pathology / Q000502:physiology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction; D012313:RNA / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D013601:T-Lymphocytes / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000097:blood* / Q000235:genetics / Q000494:pharmacology
D015704:CD4 Antigens; D015345:Oligonucleotide Probes; D016212:Transforming Growth Factor beta; D012313:RNA