Proliferation of HIV-Specific CD4, CD8 Cells Is Independent of Viral Load and Declines with Time

Duration of infection, not viral load, is responsible for the decrease in HIV-specific CD4 and CD8 cells, according to study results announced at the AIDS Vaccine 2004 International Conference in Lausanne, Switzerland.

In long-term non-progressors, as well as in people on HAART, HIV-specific CD4+ and CD8+ cells are constantly present. Chronically infected individuals do not maintain these specific T cells. To look for HIV-1 specific CD4+ Th cells, which are important in the persistence of HIV-specific CD8+ cytotoxic T lymphocytes (CTL), Dr. Yassine-Diab and colleagues enrolled 8 subjects, all of whom were treatment-naïve.

Five patients were in the acute, primary infection (PI) stage, with length of infection between 1 and 3 months. Three subjects were chronically infected (length of infection between 8 and 24 months). Viral load ranged from 1000 to 250,000 copies / mL. Peripheral blood mononuclear cells (PBMC) were screened for HIV-specific CD4+ and CD8+ response in a CFSE proliferation assay against peptides representing the entire HIV-1 consensus genome.

Results

The acutely infected patients responded to a wide array of epitopes, with both CD4+ and CD8+ proliferation. There was no response in the chronically infected individuals. Peak response appeared 45 days after infection, with 55 peptide segments recognized. In a corroborating longitudinal study done by the same group, significant loses in proliferation magnitude and number of recognized epitopes was noted in a one-month period.

Conclusions

In addition to providing information about T cell suppression as it relates to viral load and infection persistence, the study provided a large number of new epitopes that are clearly strongly immunogenic. Dr. Yassine-Diab noted these findings could be important in vaccine design, since the focus of the vaccine should be the most immunogenic part of the virus.

10/18/04

Reference
B Yassine-Diab.  Viral Infection Persistence But Not Level of Virimia Leads to Ablation Of HIV-specific CD4 and CD8 T-cells.  Abstract 10 (oral). AIDS Vaccine 2004. August 30, 2004. Lausanne, Switzerland.