Cayota A, Vuillier F, Scott-Algara D, Feuillie V, Dighiero G; International Conference on AIDS.

Int Conf AIDS. 1991 Jun 16-21; 7: 104 (abstract no. M.A.1051).

Unite d'Immunohematologie et d'Immunopathologie, Institut Pasteur, Paris, France

To study HIV replication in naive and memory CD4 T-cells, as well as, the role of different stimulatory pathways on viral replication, peripheral blood mononuclear cells (PBMCs) from 8 HIV-1-seropositive carriers (SPC) and 4 AIDS patients were positively selected into CD4+CD45RA+ and CD4+CD45RA- subsets using an "EPICS 752" cell sorter (Coultronics, Hialeah, FL). These highly-purified CD4 T-cell subsets (greater than 98%) were cultured in 96-well plates at 2.10(4) cells per well with rIL-2 (50 U/ml) to which one of the following was added: PHA (5 ug/ml), PMA (10 ng/ml), TNF-alpha (20 ng/ml), soluble anti-CD3 mAb (0.5 ug/ml) and immobilized anti-CD3 mAb (0.5 ug/ml). HIV-1 replication, as measured by p25 antigen production was examined at 4, 7, 11, 15 and 18 days of culture. Upon PHA stimulation, memory CD4 T-cells preferentially replicated the virus in the SPC group (p25 was detected at day 4). For AIDS patients, no difference in viral replication was observed in the two subsets. On the other hand, when PMA and TNF-alpha were used, p25 production was exclusively observed in memory subsets of two groups. When soluble anti-CD3 was employed, p25 production was exclusively observed in the naive subset from 2 out of 4 SPC patients. Interestingly, in these 2 patients, p25 antigen was exclusively produced by memory cells upon PMA or PHA stimulation. However, in the AIDS group, when soluble anti-CD3 was used, 3 out of 4 patients replicated HIV-1 exclusively in the memory subset and only one patient in the naive subset. When anti-CD3 and anti-CD4 were crosslinked, both naive and memory cells produced similar levels of p25 in the AIDS group. These results suggest that HIV-1 replication may depend upon the activation pathway employed, which could differentially activate HIV-1 enhancers through different cis-acting regulatory elements. This differential HIV-1 replication by CD4 T-cells depends not only on the subpopulation studied but also on the current clinical status of the patient. Studies are now being carried out in our laboratory to elucidate the role of these and other T-cell stimulatory pathways in viral replication by naive and memory CD4 T-cells.

Publication Types:

• Meeting Abstracts

Keywords:

• AIDS Vaccines
• Acquired Immunodeficiency Syndrome
• Antigens, CD4
• Antigens, CD45
• Antiretroviral Therapy, Highly Active
• CASP4 protein, human
• Caspases
• HIV
• HIV Envelope Protein gp120
• HIV Envelope Protein gp41
• HIV Infections
• HIV Seropositivity
• HIV-1
• Humans
• Phytohemagglutinins
• Receptors, HIV
• T-Lymphocyte Subsets
• T-Lymphocytes
• drug therapy
• immunology
• therapy

Other ID:

• 1105191

UI: 102182614

From Meeting Abstracts