Simian Immunodeficiency Virus Infection of CD4 + CD8 + T Cells in a Macaque with an Unusually High Peripheral CD4 + CD8 + T Lymphocyte Count

Abstract

We assessed the possible role in vivo CD4⁺ CD8⁺ T cells as a viral reservoir for simian immunodeficiency virus (SIV), in a macaque with 50% CD4⁺ CD8⁺ T cells in peripheral blood. During primary infection (day 14) of this rhesus macaque with the pathogenic SIVmac251 strain, proviruses were detected at similar frequencies in CD4⁺ CD8⁺ T cells (1/10) and CD4⁺ T cells (1/10) and at a lower frequency in CD8⁺ T cells (1/800). On day 235, no viral DNA was detected in CD8⁺ cells, despite the persistent high viral load, indicating that CD8⁺ cells do not constitute a reservoir during the chronic phase of SIV infection. Infection induced early lymphopenia of CD4⁺, CD4⁺ CD8⁺, and CD8⁺ cells; only the CD8⁺ cell population returned to initial levels and expanded further. We found that CD4⁺ CD8⁺ T cells expressed the costimulatory CD28 molecule less and were more prone to die in vitro after phytohemagglutinin/interleukin 2 stimulation than were CD4⁺ T cells. Taken together, massive death of CD4⁺ CD8⁺ T cells during acute stages of SIV infection may explain why CD8⁺ T cells did not represent a major reservoir for SIV at the onset of infection.