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Most HIV DNA in PBMC is
present in non-gut homing, resting memory CD4 T cells with a ß7-CD38-CD127high
phenotype
Presented by John Zaunders (Australia).
K.K. Koelsch1,2, Y. Xu1,2, M. Bailey1,2, K. McBride1,2, N. Seddiki1,2, K. Suzuki2, J. Murray3, D.A. Cooper1,2, A.D. Kelleher1,2, J. Zaunders2
1University of New South Wales / NCHECR, Darlinghurst, Australia, 2St Vincents Centre for Applied Medical Research, Darlinghurst, Australia, 3University of New South Wales, NCHECR / Dept. of Mathmatics, Kensington, Australia
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 2 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 from a total of 11 patients, 7 with untreated
chronic HIV infection (CHI), 2 with primary HIV infection (PHI) and 2 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 PCR.
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/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.
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