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Localization of CD8(+) cells specific for hepatitis B virus surface protein in the liver of immunize

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J Med Virol. 2008 Feb;80(2):225-32.

Localization of CD8(+) cells specific for hepatitis B virus surface protein in

the liver of immunized mice.

Qu D, Lanier G, Yuan ZH, Wen YM, CR, Ahmed R.

Department of Medical Molecular Virology, Institutes of Bio-medical Sciences,

Shanghai Medical College of Fudan University, Shanghai, People's Republic of

China.

DNA plasmids are potent inducers of long-lasting antigen-specific CTL responses.

Little is known about the distribution of antigen-specific CD8(+) T cells in the

lymphoid tissue and the non-lymphoid tissue after DNA immunization.

HBsAg-specific CD8(+) T cells in peripheral blood mononuclear cells, spleen,

lymph nodes, and the liver of Balb/c mice have been quantified after injection

with a DNA plasmid expressing the major S protein of hepatitis B virus (HBV).

The kinetics of CD8(+) T-cell responses in the circulation were measured after

priming and boosting, showing that antigen-specific CD8(+) T cells undergo first

expansion and then decline to a sustainable level in the circulation, although

the frequencies of HBsAg-specific CD8(+) T cells in the circulation were lower

than for the spleen. The greater frequencies of HBsAg-specific CD8(+) T cells

were found in the liver, whereas the largest numbers of antigen-specific CD8(+)

T cells were found in the spleen. By day 100 after priming, HBsAg-specific

CD8(+) T cells were still detected in the circulation, the spleen and the liver.

After boosting with the same plasmid DNA immunogen, HBsAg-specific CD8(+) T

cells proliferated quickly and vigorously. By 150 days after boosting,

HBsAg-specific memory CD8(+) T cells were sustained at higher levels than those

recorded after the first, primary injection, both in the spleen and the liver:

anti-HBs antibody-secreting plasma cells persisted in the bone marrow and in the

spleen, consistent with the detection of anti-HBs antibodies detected in the

blood. These findings indicate that DNA immunization has considerable potential

for inducing specific T cell responses in the liver and offers a strategy for

the development of post-exposure immunotherapy against persistent hepatitis B

infections. J. Med. Virol. 80:225-232, 2008. © 2007 Wiley-Liss, Inc.

PMID: 18098130 [PubMed - in process]

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