Inhibition of HIV replication by CD8+ T cells correlates with CD4 counts and clinical stage of disease

• Published in: Clinical and experimental immunology Vol. 97; no. 1; pp. 68 - 75
• Main Authors: GÓMEZ, A. M., SMAILL, F. M., ROSENTHAL, K. L.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.07.1994; Blackwell
• Subjects: AIDS; Biological and medical sciences; CD4-Positive T-Lymphocytes - immunology; CD8 Antigens - metabolism; CD8+ T lymphocytes; Cell Communication; Concanavalin A - pharmacology; cytotoxic T lymphocyte; disease progression; HIV; HIV Core Protein p24 - biosynthesis; HIV Infections - blood; HIV Infections - immunology; HIV Infections - microbiology; HIV Reverse Transcriptase; HIV-1 - immunology; HIV-1 - physiology; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; In Vitro Techniques; Leukocyte Count; Lymphocyte Activation; Medical sciences; RNA-Directed DNA Polymerase - metabolism; T-Lymphocyte Subsets - immunology; Virus Replication; Human; Immunopathology; Pathogenesis; Cytotoxicity; Cell cell interaction; AIDS; Immune deficiency; In vitro; Mechanism; Infection; Viral disease; In vitro replication; T-Lymphocyte; Infected cell; Inhibition
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/j.1365-2249.1994.tb06581.x

SUMMARY We sought to evaluate the relationship of CD8+ T cell‐mediated inhibition of autologous HIV replication in vitro to disease stage in HIV+ individuals. Depletion of CD8+ T cells from peripheral blood lymphocytes of 16 HIV+ subjects increased the percentage of virus‐producing cultures from 56% to 81%. CD4+ T cells were purified from 52 HIV+ individuals and cultured alone or in the presence of autologous CD8+ T cells. In 13 (25%) subjects HIV replication was only detected in the absence of CD8+ T cells (inhibition positive); in 26 (50%) viral replication occurred both in the absence and presence of CD8+ cells (inhibition negative). In the remaining 13 (25%) subjects, CD8+ T cell‐mediated inhibitory activity could not be evaluated because stimulation of their purified CD4+ T cells did not result in p24 production. In some virus culture‐negative individuals, the inability to demonstrate HIV replication was due to the presence of low numbers of CD8+ T cells that co‐purified with CD4+ T cells. Detection of inhibitory CD8+ T cells was associated with significantly higher CD4 counts and better clinical status compared with inhibition‐negative subjects. These results demonstrate that CD8+ T cell‐mediated inhibition of HIV replication correlates with disease stage, and thus may play a role in preventing disease progression. CD8+ T cells did not inhibit autologous HIV replication across a semipermeable membrane. Further, the ability of CD8+ T cells to prevent HIV replication did not correlate with lysis of autologous CD4+ T cells. Thus, CD8+ T cells inhibited autologous HIV replication in vitro through a contact mediated non‐lytic mechanism.