Evidence for Gag p24-specific CD4 T cells with reduced susceptibility to R5 HIV-1 infection in a UK cohort of HIV-exposed-seronegative subjects

• Published in: AIDS (London) Vol. 17; no. 16; pp. 2299 - 2311
• Main Authors: Eyeson, Josiah, King, Deborah, Boaz, Mark J, Sefia, Eseberuo, Tomkins, Sarah, Waters, Anele, Easterbrook, Philippa J, Vyakarnam, Annapurna
• Format: Journal Article
• Language: English
• Published: England 07-11-2003
• Subjects: Adult; AIDS/HIV; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - virology; CD8-Positive T-Lymphocytes - immunology; Cells, Cultured; Chemokine CCL4; Cytokines - metabolism; Disease Susceptibility; Female; HIV Core Protein p24 - immunology; HIV Infections - immunology; HIV Infections - virology; HIV-1 - physiology; Human immunodeficiency virus 1; Humans; Lymphocyte Activation - immunology; Macrophage Inflammatory Proteins - biosynthesis; Male; Middle Aged; Mitogens - immunology; Receptors, CCR5 - blood; Virus Replication
• ISSN: 0269-9370
• DOI: 10.1097/00002030-200311070-00004

To characterize HIV-1 Gag p24-specific CD4 cell responses in HIV-exposed-seronegative (ES) individuals.
Twelve ES individuals, of diverse ethnicity and wild type for the CCR5 Delta-32 mutation, were identified. Controls were HIV-negative blood donors. Gag p24-specific and total Vbeta+ CD4 cells that expressed MIP-1beta, IFN-gamma and IL-2 were enumerated by intracytoplasmic cytokine staining. beta-Chemokine expression was correlated with susceptibility to R5 HIV-1 infection, as measured by polymerase chain reaction for integrated HIV-1 and by p24 enzyme-linked immunosorbent assay.
Similar numbers of mitogen-stimulated and Vbeta+ MIP-1beta+, IFN-gamma+ and IL-2+ T cells were found in ES and HIV-negative control subjects. However, all ES subjects tested had an HIV Gag p24-specific MIP-1beta+, IFN-gamma+ and IL-2+ CD4 T-cell response that was rare in controls. p24-Specific cells of all ES but no control subjects could be expanded by in-vitro Ag/IL-2 stimulation, and when re-stimulated with an overlapping peptide series showed evidence of a broad CD4 cell memory response directed against multiple regions of Gag p24. Mitogen-stimulated ES CD4 cells were as susceptible to HIV infection as those from control subjects, but p24-specific IFN-gamma+ CD4 cells of six out of seven ES subjects tested were less susceptible to R5 HIV-1 infection than the counterpart fraction depleted of p24-specific IFN-gamma+ cells. The addition of blocking anti-beta-chemokine antibodies did not promote R5 HIV-1 infection of p24-specific IFN-gamma+ cells.
Specific CD4 cell immunity, characterized by a broadly directed memory Gag-p24 CD4 cell response and reduced susceptibility of specific CD4 cells to R5 HIV-1 infection, is a likely correlate of non-transmission.