Human immunodeficiency virus infection of helper T cell clones: early proliferative defects despite intact antigen-specific recognition and interleukin 4 secretion

• Published in: The Journal of clinical investigation Vol. 83; no. 6; pp. 1843 - 1848
• Main Authors: LAURENCE, J, FRIEDMAN, S. M, CHARTASH, E. K, CROW, M. K, POSNETT, D. N
• Format: Journal Article
• Language: English
• Published: Ann Arbor, MI American Society for Clinical Investigation 01.06.1989
• Subjects: Acquired Immunodeficiency Syndrome - immunology; Acquired Immunodeficiency Syndrome - metabolism; AIDS/HIV; Antigens, Differentiation, B-Lymphocyte - biosynthesis; Antigens, Differentiation, T-Lymphocyte - analysis; Antigens, Viral - immunology; Biological and medical sciences; Clone Cells - classification; Clone Cells - immunology; Epitopes - immunology; human immunodeficiency virus; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Inositol - metabolism; Interleukin-4; Interleukins - biosynthesis; Isoantigens - immunology; Lipolysis; Lymphocyte Activation; Medical sciences; Mitogens - pharmacology; Phenotype; Receptors, Fc - biosynthesis; Receptors, IgE; T-Lymphocytes - immunology; T-Lymphocytes, Helper-Inducer - classification; T-Lymphocytes, Helper-Inducer - immunology; Virus Replication; Human; Cell culture; Immunopathology; Incubation; Pathogenesis; Biological model; Retroviridae; Helper cell; AIDS; Activation; Hemopathy; Blood; Virus; Infection; B»-Lymphocyte; Interleukin 4; Mononuclear cell; Viral disease; T-Lymphocyte; Seronegativity; Human immunodeficiency virus
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/JCI114090

HIV selectively inhibited the proliferative response of clonal CD4+ T lymphocytes to alloantigen while other alloantigen-dependent responses were unperturbed. Specifically, impaired blastogenesis could be dissociated from alloantigen-specific induction of the B cell activation molecule CD23, IL-4 release, and inositol lipid hydrolysis. In addition, membrane expression of pertinent T cell receptor molecules, including CD2, CD3, and T cell antigen receptor (Ti), remained intact. Using two MHC class II-specific human CD4+ helper T cell clones, the proliferative defect was shown to be an early consequence of HIV infection, occurring within 4 d of viral inoculation and preceding increases in mature virion production. It was generalizable to three distinct methods of T cell activation, all independent of antigen-presenting cells: anti-CD3 mediated cross-linking of the CD3/Ti complex; anti-CD2 and phorbol 12-myristic 13-acetate (PMA); and anti-CD28 plus PMA. These abnormalities were not mitigated by addition of exogenous IL-2, even though expression of the IL-2 receptor (CD25) was unaltered. These studies define a selective blockade in T cell function early after HIV exposure that could serve as a model for certain in vivo manifestations of AIDS.