107. Enhancement of HIV-1-Specific CTL Responses in the Peripheral Blood during STI is Largely Due to Redistribution of Pre-Existing Virus-Specific CD8+ T Cells from the Lymph Nodes

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Session 25 Oral Abstract Session
Immunology
Session Time: Wednesday, 10 am - 12:30 pm
Room 6C

11:30 107.

Enhancement of HIV-1-Specific CTL Responses in the Peripheral Blood during STI is Largely Due to Redistribution of Pre-Existing Virus-Specific CD8+ T Cells from the Lymph Nodes
M. Altfeld*¹, J. V. Lunzen², N. Frahm², X. Yu¹, R. L. Eldridge¹, H. J. Stellbrink², and B. Walker¹
¹Partners AIDS Res. Ctr., Massachusetts Gen. Hosp. and Harvard Med. Sch., Boston, MA and ² Univ. Eppendorf, 1st Med. Klinik, Hamburg, Germany

Background: To date, most studies have focused on the characterization of HIV-1-specific immune responses in the peripheral blood (PB) of infected individuals. This study compared CTL responses in PB and lymph nodes (LN) and assessed the dynamics of these responses during antiretroviral treatment and supervised treatment interruptions.
Methods: HIV-1-specific CTL responses were characterized in paired PB and LN samples from 16 treatment naďve individuals. Follow-up samples were available from 6 individuals after 12 months of HAART, as well as after 1 interruption of treatment. CD8+ T-cell responses directed against all described optimal HIV CTL epitopes for the individual's HLA class I type were quantified using an IFN-gamma ELISPOT assay and intracellular cytokine staining. Epitope-specific T-cell clones were isolated from LN and PB.
Results: Responses against a median of 19 CTL epitopes (r: 5-32) were assessed in paired LN and PB samples from 16 individuals. HIV-specific CD8+ T-cell responses in PB and LN correlated significantly (R = 0.7). Magnitude and breadth of CD8+ T-cell responses was however significantly higher in LN (731 + 750 SFC/Mill CD8+ LNMC vs 434 + 523 SFC/million CD8+ PBMC, p < 0.01). HIV-specific CD8+ T-cell responses decreased in both compartments during HAART in the 6 subjects studied and this decline was more pronounced in the PB (550 + 661 vs 227 + 387 SFC, p= 0.04) than in the LN (792 + 949 vs 479 + 476 SFC, p = 0.14). In addition, the number of detectable CTL epitopes declined in the PB from a median of 5 (r: 3-6) epitopes per individual to a median of 1 (r: 1-6) epitope (52%). In contrast, the median number of epitopes targeted was only reduced from 6 (r: 3-6) to 5 (r: 2-6) in the LN (25%). During treatment interruption, HIV-specific CTL responses were increased significantly in the PB (p < 0.01). Interestingly, this enhancement in breadth and magnitude of responses was largely due to the re-distribution of preexisting HIV-specific CD8+ T cells from the LN to the PB.
Conclusions: HIV-specific CD8+ T cells are preferentially located in the LN with a subset of responses that is exclusively detectable in this compartment, in particular during HAART. Re-circulation of HIV-specific CD8+ T cells contributes importantly to the enhancement of virus-specific CTL responses observed during treatment interruptions in chronically infected individuals.

Š2002 9^th Conference on Retroviruses and Opportunistic Infections