AEGiS-11IAC: High HIV-1 nef-specific precursor CTL frequencies in recent seroconverters in India.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

High HIV-1 nef-specific precursor CTL frequencies in recent seroconverters in India.

Int Conf AIDS 1996 Jul 7-12; 11:37 (abstract no. Th.A.147)
Paranjape RS, Lubaki N, Mehendale S, Quinn T, Siliciano R, Bollinger R; National AIDS Research Institute, Bhosari, Pune, India. Fax: 212-791071. E-mail: root@nar.ernet.in.

OBJECTIVE: To estimate frequencies of precursors of cytotoxic T lymphocytes specific for different HIV-1 proteins in persons who have seroconverted recently.

METHODS: Under a collaborative study between National AIDS Research Institute, India and Johns Hopkins University, USA, we have studied precursor frequencies of gag, nef and env specific CTLs (pCTL) in recently seroconverted persons. Precursor frequencies of CTL were measured by Limiting Dilution Assay (LDA). Immunophenotyping for CD4+ and CD8+ cell count, and quantitative PCR for determining viral burden in plasma were also carried out. CTL assays were carried out on frozen cell specimens at a later date. The lymphocytes from patients were cultured at 250 to 16000 cells per well concentration in the presence of 25000 irradiated heterologous feeder cells and 1600 stimulator cells i.e. UV-psoralen treated homologous B cell line infected with HIV antigen expressing vaccinia construct. On day 14, cells from each well were split into four wells and a standard 4 hour (51)Chromium release assay was performed. Percentage of wells showing CTL activity was calculated for each cell concentration. Precursor frequencies were calculated using maximum likelihood model.

RESULTS: The time interval between seroconversion and CTL assays in six patients under study ranged from 81 days to 339 days. Precursor frequencies of nef, gag and env specific CTLs of varied between 81 and 293, 112 and 436 and 59 and 213 per 10(6) lymphocytes respectively. There was no apparent relationship between viral burden and pCTLs specific to HIV antigens. Nef-specific pCTL values were higher in persons tested closer to seroconversion. Persons with high nef-pCTL values also had low CD4 cell counts.

CONCLUSIONS: Nef, a regulatory HIV-1 protein, plays an important role in virus multiplication. Possible relationship between nef specific CTL and the progression of the disease needs to be studied further. The importance of the relationship between nef-specific CTL and CD4 cell counts and the time from seroconversion vis a vis progress of infection and clinical disease needs to be investigated further.

Keywords: AEGIS, HIV-1, HIV Antigens, Viral Load, T-Lymphocytes, Cytotoxic, CD4 Lymphocyte Count, Acquired Immunodeficiency Syndrome, Virus Replication, Antigens, CD8, Antigens, CD4, India, Human, virology, ICA11

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