Cutting Edge: JAK3 Activation and Rescue of T Cells from HIV gp120-Induced Unresponsiveness

• Published in: The Journal of immunology (1950) 1998-06, Vol.160 (12), p.5697-5701
• Main Authors: Selliah, Nithianandan, Finkel, Terri H
• Format: Article
• Language: English
• Subjects: Adult; AIDS/HIV; Antibodies, Monoclonal - immunology; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - virology; Cell Division; Enzyme Activation; HIV Envelope Protein gp120 - immunology; HIV Infections - immunology; HIV-1; Humans; In Vitro Techniques; Janus Kinase 1; Janus Kinase 3; Lymphocyte Activation - immunology; Peptide Fragments - immunology; Protein-Tyrosine Kinases - metabolism; Receptors, Antigen, T-Cell - immunology; Receptors, Interleukin-2 - biosynthesis; Receptors, Interleukin-2 - immunology; Signal Transduction
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.160.12.5697

In early HIV disease, immunodeficiency is characterized by the inability of CD4+ T cells to produce a critical cytokine, IL-2, and to express the receptor for IL-2 (IL-2R) in response to antigenic or mitogenic stimulation. The shared common gamma-chain (gamma(c)) of IL-2R and its associated Janus kinase, JAK3, are indispensable for normal T cell function. Here, we show that the inhibition of IL-2R expression and proliferation induced by ligation of CD4 by HIV envelope glycoprotein, gp120, is correlated with inhibition of expression and activation of JAK3. Stimulation through the gamma(c)-related cytokine receptors restores JAK3 expression and activation and rescues CD4-mediated T cell unresponsiveness. Collectively, these data argue that inhibition of JAK3 expression and activation may, in part, explain the T cell dysfunction seen in early HIV disease. In addition, rescue from gp120-mediated T cell unresponsiveness by activation of JAK3 suggests a novel therapeutic approach for enhancing immune function in HIV disease.