Differential dynamics of CD4(+) and CD8(+) T-lymphocyte proliferation and activation in acute simian immunodeficiency virus infection

Although lymphocyte turnover in chronic human immunodeficiency virus and si mian immunodeficiency virus (SN) infection has been extensively studied, th ere is little information on turnover in acute infection. We carried out a prospective kinetic analysis of lymphocyte proliferation in 13 rhesus macaq ues inoculated with pathogenic SN. A short-lived dramatic increase in circu lating 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(+) natu ral killer cells accounted for >85% of proliferating lymphocytes at peak pr oliferation. In contrast, there was little change in the percentage of Ki-6 7(+) CD4(+) T lymphocytes during acute infection, although transient increa ses 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 e xpressing 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 base line 6 months after SIV infection. Increased CD8(+) T-lymphocyte proliferat ion was associated with cell expansion, paralleled the onset of SIV-specifi c 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.