AEGiS-11IAC: CD8+ cell suppression of HIV occurs in lymphoid tissues as well as in peripheral blood of HIV-infected individuals.

11th International AIDS Conference


Vancouver, British Columbia — July 7-12, 1996

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CD8+ cell suppression of HIV occurs in lymphoid tissues as well as in peripheral blood of HIV-infected individuals.

Int Conf AIDS 1996 Jul 7-12; 11:210 (abstract no. Th.A.102)
Blackbourn DJ, Mackewicz CE, Barker E, Hunt TK, Herndier B, Haase AT, Ramachandran B, Levy JA; Cancer Research Institute, University of California-San Francisco, San Francisco, CA, USA.

OBJECTIVE: To compare the noncytotoxic anti-HIV activity of CD8+ cells from the lymphoid tissues and peripheral blood of HIV-infected individuals at different clinical states.

METHODS: Five HIV-infected patients at different stages of disease were studied. CD8+ cells were isolated from stimulated mononuclear cells (MC) from lymphoid tissue (LMC) and peripheral blood (PBMC). The CD8+ cells were cocultured at multiple CD8+:CD4+ cell ratios with PHA-stimulated autologous CD4+ cells from the subjects. Inhibition of HIV replication by greater than or equal to 90% was measured. HIV load in LMC and PBMC was determined by infectious center assay. In situ hybridization detected virus replication in the lymphoid tissues and PBMC.

RESULTS: CD8+ cells from both the PBMC and LMC of two HIV-infected long term survivors suppressed HIV replication at a CD8+:CD4+ cell ratio of at least 0.1. CD8+ cells from the PBMC of a third asymptomatic subject suppressed HIV replication at a CD8+:CD4+ cell ratio of 0.05; his LMC CD8+ cells showed this antiviral response at a ratio of 0.25 CD8+ cells from two patients with progressive HIV-related disease showed lower antiviral activity. The CD8+ cells from the PBMC of one patient with 213 CD4+ cells/microliter suppressed HIV replication at a CD8+:CD4+ cell ratio of 0.1, but his LMC CD8+ cells failed to suppress HIV replication. The CD8+ cells of the PBMC from the AIDS patient (87 CD4+ cells/microliter) inhibited HIV replication by only 81% at a CD8+:CD4+ cell ratio of 1.0. Lower ratios with both PBMC and LMC CD8+ cells showed enhancement of HIV replication. The viral burden of the lymphoid tissue of the three healthy patients was greater than that of the peripheral blood (1-3 log 10). The viral burden of the pre-AIDS patient was 10-fold higher in the peripheral blood and the same in both compartments of the AIDS patient. In situ hybridization studies supported these results.

CONCLUSIONS: CD8+ cells from the lymphoid tissue of HIV-infected individuals suppress HIV replication, consistent with the antiviral activity of CD8+ cells from the PBMC. The strength of this antiviral response by lymphoid CD8+ cells appears to correlate best with the clinical state. CD8+ cells in both the lymphoid tissue and peripheral blood may provide significant control of HIV replication in vivo.

Keywords: AEGIS, HIV, Antigens, CD8, Lymphoid Tissue, HIV Infections, Virus Replication, Antigens, CD4, Acquired Immunodeficiency Syndrome, Viral Load, HIV Core Protein p24, HIV Seronegativity, Human, virology, immunology, ICA11KWDaegis,hiv,antigens,cd8,lymphoidtissue,hivinfections,virusreplication,antigens,cd4,acquiredimmunodeficiencysyndrome,viralload,hivcoreproteinp24,hivseronegativity,human,virology,immunology,ica11

960707
ThA102

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