AEGiS-11IAC: Ability of CD8+ cells to suppress HIV replication is dependent on the presence of cells expressing the CD28 molecule.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

Ability of CD8+ cells to suppress HIV replication is dependent on the presence of cells expressing the CD28 molecule.

Int Conf AIDS 1996 Jul 7-12; 11:210 (abstract no. Th.A.101)
Edward B, Bossart KN, Fujimura S, Levy JA; Cancer Research Institute, University of California-San Francisco, San Francisco, CA, USA. Fax: (415) 476-8365.

OBJECTIVE: To determine if CD8+ cells expressing the CD28 molecule are involved in suppression of HIV replication.

METHODS: CD8+ cells were isolated from peripheral blood mononuclear cells (PBMC) of HIV-infected subjects and cultured for 3 days in medium containing 10% natural IL-2 with or without PHA or anti-CD3 antibodies. In studies evaluating the requirement for CD28+ cells in suppression of HIV, CD28+ cells were removed from the CD8+ cell population with antibody-specific magnetic beads. Isolated CD8+ cells either expressing or not expressing CD28 were evaluated for their ability to suppress HIV-1SF33 replication in CD4+ cells by greater than or equal to 90%. Finally, the effect of antibody to CD28 on CD8+ cell antiviral response was evaluated. For all studies, expression of the CD28 molecule on CD8+ cells was monitored by flow cytometry.

RESULTS: Initially a correlation was observed in the ability of PHA-stimulated CD8+ cells to suppress HIV and the percentage of CD8+ cells expressing CD28. Of the 11 asymptomatic subjects evaluated, CD8+ cells from 4 individuals required CD8:CD4+ cell ratios greater than 1 to suppress HIV replication by 90 %. Of these CD8+ cells only 59-64 % were CD28+. CD8+ cells from the 7 other individuals required CD8+:CD4+ cell ratios less than 0.5 to suppress HIV replication and the percentage of CD8+CD28+ cells ranged from 91-97%. CD8+ cells from progressors (n=11) had a decreased ability to suppress. HIV replication than the asymptomatic subjects (CD8:CD4+ cell ratios of 3.0 vs. 0.75 respectively), and the percentage of CD8+ cells expressing CD28 was lower in progressors (68% vs. 82%). Removal of CD28+ cells from unstimulated CD8+ cells from 2 asymptomatic individuals (CD8+CD28+ cells went from 51% to 1% and 30% to 2%) nearly eliminated the ability of the cells to suppress HIV replication. Treatment of CD8+ cells during stimulation with antibody to CD28 increased the ability of the cells to suppress HIV replication.

CONCLUSION: CD8+ cells expressing CD28 are primarily involved in suppression of HIV replication and the engagement of the CD28 molecule on CD8+ cells may enhance this antiviral response.

Keywords: AEGIS, Antigens, CD28, Antigens, CD8, HIV, Virus Replication, CD8-Positive T-Lymphocytes, HIV Infections, CD4-Positive T-Lymphocytes, Antigens, CD3, T-Lymphocyte Subsets, Antigens, CD4, Receptors, Interleukin-2, Interleukin-2, T-Lymphocytes, Cytotoxic, T-Lymphocytes, Suppressor-Effector, Cells, HIV Core Protein p24, virology, ICA11

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