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 2

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(a) Magnitude of epitope-specific CD8+ T cell responses in PB and LNs. M...
(a) Magnitude of epitope-specific CD8+ T cell responses in PB and LNs. Magnitudes of responses in each compartment are given as SFCs/million CD8+ T cells, and presented as box plots showing the median and the 5th/95th percentile. Statistical significance of differences between the magnitude of responses to individual CTL epitopes in PB and LNs was calculated by two-tailed Student t test. (b) Breadth of epitope-specific CD8+ T cell responses in PB and LNs. Breadth of CD8+ T cell responses in the 15 individuals studied is presented as a box plot for each compartment, showing the median and the 5th/95th percentile. Statistical significance of differences between the breadth of responses in PB and LNs was calculated by two-tailed Student t test. (c) Contribution and hierarchy of individual HIV-1–specific CTL epitopes to the total virus-specific response in PB and LNs in four representative individuals (A–D). The individual epitopes recognized are specified in the legend and described by the restricting HLA class I allele, the first and last amino acids, the length of the peptide, and the HIV-1 protein.