Most CD4+ T cells from human immunodeficiency virus-1 infected patients can undergo prolonged clonal expansion

• Published in: The Journal of clinical investigation Vol. 84; no. 5; pp. 1637 - 1643
• Main Authors: LANGHOFF, E, MCELRATH, J, BOS, H. J, PRUETT, J, GRANELI-PIPERNO, A, COHN, Z. A, STEINMAN, R. M
• Format: Journal Article
• Language: English
• Published: Ann Arbor, MI American Society for Clinical Investigation 01.11.1989
• Subjects: Acquired Immunodeficiency Syndrome - blood; AIDS/HIV; Antigens, CD - analysis; Antigens, Differentiation, T-Lymphocyte; Biological and medical sciences; CD4 Antigens - analysis; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - microbiology; CD4-Positive T-Lymphocytes - pathology; CD8 Antigens; Cell Division; Clone Cells - pathology; Dendritic Cells - physiology; HIV-1 - genetics; HIV-1 - growth & development; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Interleukin-2 - pharmacology; Male; Medical sciences; Nucleic Acid Hybridization; Phytohemagglutinins - pharmacology; RNA, Messenger - analysis; RNA, Viral - analysis; Infection; Human; Cell proliferation; AIDS; Viral disease; T-Lymphocyte
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/JCI114341

We have addressed the capacity of HIV-1 infection to alter the growth of primary CD4+ T cells, but at the clonal level. Single T cells were expanded in the presence of PHA, IL-2, and small numbers of accessory dendritic cells. We report two new findings. First, T cells from seropositive individuals, even those with AIDS and markedly reduced CD4+ counts, exhibit a normal cloning efficiency, and proliferative capacity. This result is in contrast to two prior reports of a low cloning efficiency in CD4+ T cells from HIV-1-infected patients. Second, when we added high doses of exogenous HIV-1 to T cell clones from control subjects, we observed infection but not cytotoxicity or loss of CD4+ cells, following addition of virus stocks at days 0, 3, and/or 7 of clonal growth. The same HIV-1 isolates markedly reduced CD4+ T cells in bulk mononuclear cultures. When tested at day 11, HIV-1 mRNA was expressed in some cells of exogenously infected clones by in situ hybridization; when tested at day 18, several clones could transactivate a TAT-sensitive cell line. These findings suggest that the loss of CD4+ T cells in infected individuals is not the inevitable result of the activation of latent infection, or spread of a productive infection, during clonal growth.