Expansion of pre-existing, lymph node-localized CD8+ T cells during supervised treatment interruptions in chronic HIV-1 infection
Marcus Altfeld, … , Hans-Juergen Stellbrink, Bruce D. Walker
Marcus Altfeld, … , Hans-Juergen Stellbrink, Bruce D. Walker
Published March 15, 2002
Citation Information: J Clin Invest. 2002;109(6):837-843. https://doi.org/10.1172/JCI14789.
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Article Immunology

Expansion of pre-existing, lymph node-localized CD8+ T cells during supervised treatment interruptions in chronic HIV-1 infection

Abstract

To date, most studies have focused on the characterization of HIV-1–specific cellular immune responses in the peripheral blood (PB) of infected individuals. Much less is known about the comparative magnitude and breadth of responses in the lymphoid tissue. This study analyzed HIV-1–specific CD8+ T cell responses simultaneously in PB and lymph nodes (LNs) of persons with chronic HIV-1 infection and assessed the dynamics of these responses during antiretroviral treatment and supervised treatment interruption (STI). In untreated chronic infection, the magnitude of epitope-specific CD8+ T cell activity was significantly higher in LNs than in PB. Responses decreased in both compartments during highly active antiretroviral therapy, but this decline was more pronounced in PB. During STI, HIV-1–specific CD8+ T cell responses in PB increased significantly. Enhancement in breadth and magnitude was largely due to the expansion of pre-existing responses in the LNs, with new epitopes infrequently targeted. Taken together, these data demonstrate that HIV-1–specific CD8+ T cells are preferentially located in the LNs, with a subset of responses exclusively detectable in this compartment. Furthermore, the enhanced CD8+ T cell responses observed during STI in chronically infected individuals is largely due to expansion of pre-existing virus-specific CD8+ T cells, rather than the induction of novel responses.

Authors

Marcus Altfeld, Jan van Lunzen, Nicole Frahm, Xu G. Yu, Claus Schneider, Robert L. Eldridge, Margaret E. Feeney, Dirk Meyer-Olson, Hans-Juergen Stellbrink, Bruce D. Walker

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Figure 3

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Decline of HIV-1–specific CD8+ T cell responses to individual CTL epitop...
Decline of HIV-1–specific CD8+ T cell responses to individual CTL epitopes upon treatment with HAART in the five individuals studied in the PB (left) and LNs (right). Epitope-specific CD8+ T cell responses are shown prior to the initiation of HAART (pre-HAART) and after 12 months on HAART (on HAART). Magnitudes of responses are given as SFCs/million CD8+ T cells, and each line demonstrates the evolution of responses in an individual CTL epitope. Mean magnitude of HIV-1–specific CD8+ T cell responses ± SD are shown before HAART and after 12 months on HAART, as is the total number of recognized CTL epitopes (numbers inside boxes) in the five individuals. Statistical significance of differences between the magnitude of responses to individual CTL epitopes before HAART and after 12 months on HAART were calculated by two-tailed Student t test.