Emergence and Kinetics of Simian Immunodeficiency Virus-Specific CD8 + T Cells in the Intestines of Macaques during Primary Infection

Author:

Veazey Ronald S.12,Gauduin Marie-Claire1,Mansfield Keith G.1,Tham Irene C.1,Altman John D.3,Lifson Jeffrey D.4,Lackner Andrew A.1,Johnson R. Paul15

Affiliation:

1. New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts 017721;

2. Tulane Regional Primate Research Center, Tulane University, Covington, Louisiana 704332;

3. Emory Vaccine Center at Yerkes, Emory University School of Medicine, Atlanta, Georgia 303223;

4. SAIC, NCI-Frederick Cancer Research and Development Center, Frederick, Maryland 217024; and

5. Infectious Disease Unit and Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 021295

Abstract

ABSTRACT In this report, three Mamu-A*01 + rhesus macaques were examined to compare the emergence of simian immunodeficiency virus (SIV)-specific CD8 + T cells in the intestines and blood in early SIV infection using a major histocompatibility complex class I tetramer complexed with the Gag 181–189 peptide. Fourteen days after intravenous inoculation with SIVmac251, large numbers of SIV Gag 181–189 -specific CD8 + T cells were detected in the intestinal mucosa (3.1 to 11.5% of CD3 + CD8 + lymphocytes) as well as in the blood (3.1 to 13.4%) of all three macaques. By 21 days postinoculation, levels of tetramer-binding cells had dropped in both the intestines and blood. At day 63, however, levels of SIV Gag 181–189 -specific CD8 + T cells in the intestines had rebounded in all three macaques to levels that were higher (8.6 to 18.7%) than those at day 21. In contrast, percentages of tetramer-binding cells in the peripheral blood remained comparatively stable (2.5 to 4.5%) at this time point. In summary, SIV Gag 181–189 -specific CD8 + T cells appeared in both the intestinal mucosa and peripheral blood at a comparable rate and magnitude in primary SIV infection. Given that the intestine is a major site of early viral replication as well as the site where most of the total body lymphocyte pool resides, these data indicate that it is also an early and important site of development of antiviral immune responses.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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