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Journal of Virology, September 2000, p. 8413-8424, Vol. 74, No. 18
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Differential Dynamics of CD4+ and CD8+ T-Lymphocyte Proliferation and Activation in Acute Simian Immunodeficiency Virus Infection

Amitinder Kaur,1,* Corrina L. Hale,1 Saroja Ramanujan,2 Rakesh K. Jain,2 and R. Paul Johnson1,3

Division of Immunology, New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772,1 and Department of Radiation Oncology2 and Infectious Disease Unit and Partners AIDS Research Center,3 Massachusetts General Hospital, Charlestown, Massachusetts 02129

Received 20 April 2000/Accepted 15 June 2000

Although lymphocyte turnover in chronic human immunodeficiency virus and simian immunodeficiency virus (SIV) infection has been extensively studied, there is little information on turnover in acute infection. We carried out a prospective kinetic analysis of lymphocyte proliferation in 13 rhesus macaques inoculated with pathogenic SIV. A short-lived dramatic increase in circulating Ki-67+ lymphocytes observed at 1 to 4 weeks was temporally related to the onset of SIV replication. A 5- to 10-fold increase in Ki-67+ CD8+ T lymphocytes and a 2- to 3-fold increase in Ki-67+ CD3- CD8+ natural killer cells accounted for >85% of proliferating lymphocytes at peak proliferation. In contrast, there was little change in the percentage of Ki-67+ CD4+ T lymphocytes during acute infection, although transient increases in Ki-67- and Ki-67+ CD4+ T lymphocytes expressing CD69, Fas, and HLA-DR were observed. A two- to fourfold decline in CD4+ T lymphocytes expressing CD25 and CD69 was seen later in SIV infection. The majority of Ki-67+ CD8+ T lymphocytes were phenotypically CD45RA- CD49dhi Fashi CD25- CD69- CD28- HLA-DR- and persisted at levels twofold above baseline 6 months after SIV infection. Increased CD8+ T-lymphocyte proliferation was associated with cell expansion, paralleled the onset of SIV-specific cytotoxic T-lymphocyte activity, and had an oligoclonal component. Thus, divergent patterns of proliferation and activation are exhibited by CD4+ and CD8+ T lymphocytes in early SIV infection and may determine how these cells are differentially affected in AIDS.

* Corresponding author. Mailing address: Division of Immunology, New England Regional Primate Research Center, One Pinehill Dr., Southborough, MA 01772. Phone: (508) 624-8169. Fax: (508) 624-8172. E-mail: amitinder_kaur{at}hms.harvard.edu.

Journal of Virology, September 2000, p. 8413-8424, Vol. 74, No. 18
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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