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Phenotypic Differences in Homing Receptor Expression on SIV-specific CD8+ T Cells Elicited by Intravenous vs Subcutaneous Inoculation with Single-cycle SIV
A Rahmberg1, W Neidermyer1, S Ng1, A Carville1, K Mansfield1, M Piatak2, J Lifson2, P Johnson1, and David Evans*1
1New England Primate Res Ctr, Harvard Med Sch, Southborough, MA, US and 2SAIC, Frederick, MD, US and NCI, Frederick, MD, US
Background: The gut-associated lymphoid tissues (GALT)
represent an important compartment for early virus replication and destruction
of CD4+ lymphocytes. Thus, vaccine strategies designed to maximize
immunity in mucosal compartments may be more effective at preventing or
containing HIV-1 replication at the earliest stages of infection.
Methods: To determine whether the site of
immunization influences the mucosal homing properties of virus-specific T cell
responses, separate groups of 8 rhesus macaques were immunized by intravenous vs
subcutaneous injection on weeks 0, 8, and 24 with vesicular stomatitis virus (VSV)
G trans-complemented single-cycle simian immunodeficiency virus (SIV) (VSV G
scSIV). The phenotypic properties of Mamu-A*01-Gag181-189-,
Mamu-A*01-Tat28-35-, and Mamu-A*02-Nef159-167-specific
CD8+ T cells elicited by each route of immunization were determined
by polychromatic flow cytometry using an 8-color tetramer panel that included
antibodies to lymphocyte homing and memory markers.
Results: Significant changes in CCR7 expression were
observed as virus-specific CD8+ T cells transitioned from effector
to central, and from central to effector, memory phenotypes after each
inoculation. While the magnitude of SIV-specific CD8+ T cell
responses did not differ significantly for intravenous vs subcutaneous
inoculation, the percentages of virus-specific CD8+ T cells that
expressed the mucosal homing receptor a4b7 were significantly higher for intravenous than
for subcutaneous inoculated animals. Conversely, the percentages of
virus-specific CD8+ T cells that expressed E-selectin ligand, a
cutaneous homing marker, were significantly higher for subcutaneous than for intravenously
inoculated animals. Nevertheless, both routes of immunization resulted in
similar SIV-specific T cell frequencies in rectal biopsies.
Conclusions: Despite inducing polarized homing
receptor expression on CD8+ T cells in the peripheral blood, the
site of inoculation with VSV G scSIV did not result in detectable differences
in the trafficking of virus-specific CD8+ T cells to GALT. These
observations suggest that although the site of immunization can influence the
profile of homing markers on virus-specific T cells, mucosal trafficking is not
an all-or-none phenomenon, and vaccination at peripheral sites can induce
cellular immune responses in mucosal compartments.
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