AEGiS-11IAC: IL-15 supports anti-HIV-1 cytotoxic T cell and NK activity with less induction of HIV-1 replication than IL-2.

11th International AIDS Conference


Vancouver, British Columbia — July 7-12, 1996

Print this Article


IL-15 supports anti-HIV-1 cytotoxic T cell and NK activity with less induction of HIV-1 replication than IL-2.

Int Conf AIDS 1996 Jul 7-12; 11:5 (abstract no. Mo.A.141)
Skolnik PR, Wang A, Fabry J, Lieberman J; New England Medical Center, Boston, MA. Fax: 617-636-3216. E-mail: paul.skolnik@es.nemc.org.

OBJECTIVE: To determine the effects of interleukin-15 (IL-15) on HIV-1 replication and specific anti-HIV cytotoxic T cell (CTL) activity in comparison with IL-2, which shares beta and gamma receptor chains with IL-15.

METHODS: IL-15- or IL-2-prestimulated PBMC from HIV-seronegative donors (N=6) were infected with HIV-1LAI or a clinical isolate and cultured with IL-15 or IL-2 (0.65pM-65nM). HIV-1 replication (p24 antigen in supernatant fluids) was measured after 7 days of culture. For CTL assays, PBMC from HIV-seropositive patients (N=6), with CTL against known MHC-restricted peptide epitopes in gag, pol, env and nef, were used as effector cells with the relevant epitope presented by autologous EBV-transformed target cells, in a 51Cr release assay. Natural killer (NK) activity was measured against K562 targets. Cultures were performed in the presence of IL-15 or IL-2 (0.65pM-65nM).

RESULTS: IL-15 (.065-.65nM) induced less p24 antigen production than IL-2 in PBMC acutely-infected with HIV-1LAI or a clinical isolate (p24: 1-80 ng/ml and 140-210 ng/ml, respectively; p is less than 0.01). IL-15 and IL-2 supported anti-HIV CTL and NK activity equally well for all epitopes. At 0.4nM, results for IL-15 and IL-2 were 12.1 plus or minus 7.6 and 13.4 plus or minus 8.8 (env); 22.2 plus or minus 7.1 and 12.8 plus or minus 7.0 (pol); 22.6 plus or minus 6.6 and 22.9 plus or minus 6.2 (gag); 7.6 plus or minus 4.6 and 6.7 plus or minus 6.0 (nef); and 37.4 plus or minus 19.6 and 28.1 plus or minus 8.4 (NK).

CONCLUSIONS: IL-15 and IL-2 support specific anti-HIV CTL and NK activity equally well, but IL-15 induces substantially less HIV-1 replication than IL-2. Therefore, IL-15 is a good candidate for immunotherapy to bolster immune responses and CD4 cell number in HIV-seropositive persons.

Keywords: AEGIS, Interleukin-15, T-Lymphocytes, Cytotoxic, HIV-1, Interleukin-2, Virus Replication, HIV Antigens, HIV, HIV Infections, HIV Seropositivity, Epitopes, Human, virology, ICA11KWDaegis,interleukin-15,t-lymphocytes,cytotoxic,hiv-1,interleukin-2,virusreplication,hivantigens,hiv,hivinfections,hivseropositivity,epitopes,human,virology,ica11

960707
MoA141

Copyright © 1996 - International AIDS Society (IAS). Reproduction of this abstract (other than one copy for personal reference) must be cleared through the IAS.