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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Immunotargets+Ther
2017 ; 6
(ä): 39-49
Nephropedia Template TP
Immunotargets Ther
2017[]; 6
(ä): 39-49
PMID28670575
show ga
Whether inflation of CD8(+) memory T (mT) cells, which is often derived from
repeated prime-boost vaccinations or chronic viral infections in the elderly,
would affect late CD8(+) T-cell immunity is a long-standing paradox. We have
previously established an animal model with mT-cell inflation by transferring
ConA-stimulated monoclonal CD8(+) T cells derived from Ova-specific
T-cell-receptor transgenic OTI mice into irradiation-induced lymphopenic B6 mice.
In this study, we also established another two animal models with mT-cell
inflation by transferring, 1) ConA-stimulated monoclonal CD8(+) T cells derived
from lymphocytic choriomeningitis virus glycoprotein-specific T-cell-receptor
transgenic P14 mice, and 2) ConA-stimulated polyclonal CD8(+) T cells derived
from B6.1 mice into B6 mice with irradiation-induced lymphopenia. We vaccinated
these mice with recombinant Ova-expressing Listeria monocytogenes and Ova-pulsed
dendritic cells, which stimulated CD4(+) T cell-independent and CD4(+)
T-cell-dependent CD8(+) T-cell responses, respectively, and assessed Ova-specific
CD8(+) T-cell responses by flow cytometry. We found that Ova-specific CD8(+)
T-cell responses derived from the latter but not the former vaccination were
significantly reduced in mice with CD8(+) mT-cell inflation compared to wild-type
B6 mice. We determined that naïve CD8(+) T cells purified from splenocytes of
mice with mT-cell inflation had defects in cell proliferation upon stimulation in
vitro and in vivo and upregulated T-cell anergy-associated Itch and GRAIL
molecules. Taken together, our data reveal that CD8(+) mT-cell inflation renders
compromised CD4(+) T-cell-dependent CD8(+) T-cell immunity via naïve T-cell
anergy, and thus show promise for the design of efficient vaccines for elderly
patients with CD8(+) mT-cell inflation.