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  • Open Access

Most HIV DNA in PBMC is present in non-gut homing, resting memory CD4+ T cells with a ß7-CD38-CD127 high phenotype

  • KK Koelsch1, 2,
  • Y Xu1, 2,
  • M Bailey1, 2,
  • K McBride1, 2,
  • N Seddiki1, 2,
  • K Suzuki2,
  • J Murray3,
  • DA Cooper1, 2,
  • AD Kelleher1, 2 and
  • J Zaunders2Email author
Journal of the International AIDS Society201013(Suppl 3):O2

https://doi.org/10.1186/1758-2652-13-S3-O2

Published: 04 November 2010

Keywords

Lymphoid TissueMemory CellCell DepletionHoming CellSecondary Lymphoid Tissue

Background

Recent studies report that most CD4+ T cell depletion occurs in gut-associated lymphoid tissue (GALT), inferring that most viral replication occurs in these tissues. Memory CD4 T lymphocytes in peripheral blood comprise two main subsets: those with integrins α4ß7 that recirculate through GALT; and those with α4ß1 that do not access GALT. We tested the hypothesis that α4ß7+ CD4 T cells are preferentially infected with HIV DNA.

Methods

Peripheral blood or leukopheresis packs were collected from a total of 11 patients: seven with untreated chronic HIV infection (CHI); two with primary HIV infection (PHI); and two with long-term fully suppressed CHI. CD4 T cells were first isolated by negative selection. Then further FACS sorted into highly purified subsets of CD3+CD4+CD45RO+ cells: ß7+ vs. ß7-; CD25+CD127dim Treg vs CD127high; CD27+ vs. CD27-; and CD38+ vs. CD38- subsets. DNA was extracted and total HIV DNA copies quantified by real-time Polymerase Chain Reaction.

Results

Approximately 90% of HIV DNA copies in PBMC from the three groups were in CD3+CD4+CD45RO+ memory cells. Further subdivision of these memory CD4 T cells in early and/or untreated CHI found that a median 80% of this HIV DNA was found in ß7- non-gut homing cells. Similar results were obtained in PHI and in fully suppressed CHI. A median 8% of HIV DNA in early untreated CHI was found in highly purified Tregs, with the majority in CD127high memory cells. Only 9% of HIV DNA was found in CD38+ activated memory, while 32% was found in effector memory CD27- cells.

Conclusions

Our results demonstrate that the majority of the HIV reservoir in PBMC is present in non-gut homing memory CD4 T cells with a resting CD127highCD38-CD27+ phenotype. These cells recirculate preferentially through secondary lymphoid tissue, but not GALT. These results are important for the design of therapy regimens targeting the HIV reservoir.

Authors’ Affiliations

(1)
University of New South Wales / National Centre in HIV Epidemiology and Clinical Research (NCHECR), Darlinghurst, Australia
(2)
St Vincent’s Centre for Applied Medical Research, Darlinghurst, Australia
(3)
Department of Mathematics, University of New South Wales, NCHECR, Kensington, Australia

Copyright

© Zaunders et al; licensee BioMed Central Ltd. 2010

This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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