title: Differential dynamics of CD4(+) and CD8(+) T-lymphocyte proliferation and activation in acute simian immunodeficiency virus infection.
abstract: 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(-) CD49d(hi) Fas(hi) 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.
authors.affiliation: Division of Immunology, New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772, USA. amitinder_kaur@hms.harvard.edu
authors.forename: A
authors.initials: A
authors.lastname: Kaur
authors.forename: C L
authors.initials: CL
authors.lastname: Hale
authors.forename: S
authors.initials: S
authors.lastname: Ramanujan
authors.forename: R K
authors.initials: RK
authors.lastname: Jain
authors.forename: R P
authors.initials: RP
authors.lastname: Johnson
mesh_terms: D000208:Acute Disease; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division; D019394:Ki-67 Antigen / Q000378:metabolism; D007694:Killer Cells, Natural / Q000473:pathology; D016131:Lymphocyte Subsets / Q000473:pathology; D008253:Macaca mulatta; D011446:Prospective Studies; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000473:pathology; D015302:Simian Immunodeficiency Virus / Q000276:immunology* / Q000502:physiology
chemical_list: D019394:Ki-67 Antigen; D011948:Receptors, Antigen, T-Cell