High Levels of Human Immunodeficiency Virus Infection of CD8 Lymphocytes Expressing CD4 In Vivo

Abstract

Human immunodeficiency virus (HIV)-infected CD8 lymphocytes have been reported in vivo؉ CD4 ؊ lymphocytes (undetectable in seven of nine individuals; P < 0.01) and approached that of CD4 lymphocytes from the same individuals (median, 3,660 HIV LTR copies/10 6 cells). CD8 bright CD4 dim lymphocytes represented 0.8 to 3.3% of total CD8 lymphocytes and were most prevalent in the memory subset. Thus, HIV-infected CD8 lymphocytes commonly circulate in HIV-infected individuals and are generated through infection of activated CD8 lymphocytes rather than through export of intrathymically infected precursors. The high level of infection of CD8 bright CD4 dim lymphocytes could have a direct role in the decline in CD8 lymphocyte function that accompanies HIV disease progression.

Human Immunodeficiency Virus Nef Induces Rapid Internalization of the T-Cell Coreceptor CD8αβ

“…However, as previously reported, CD8␣␤/CD4 down-regulation alone cannot explain Nef-mediated impaired T-cell development, and other functions of Nef and/or HIV are needed for its induction of thymic depletion (61). Although CD8␣␤ ϩ CD4 low T lymphocytes account for a minor fraction of peripheral blood CD8 lymphocytes (Ͻ5%), HIV patients were found to harbor high levels of infection in this CD8 subset, approaching those found in CD4 lymphocytes, whereas CD8␣␤ ϩ CD4 Ϫ T lymphocytes showed very low or even undetectable viral DNA loads (12). Possibly, the ability of HIV to infect this activated CD8 ϩ population may contribute to the decline in CD8 lymphocyte function which is at present predominantly ascribed to the lack of CD4 lymphocyte help and viral escape (reviewed by McMichael and Rowland-Jones [46]).…”

“…This infection route can occur during intrathymic CD8 lymphocyte development, at the CD4 ϩ CD8 ϩ double positive stage (14), or upon activation of the mature CD8 lymphocyte, which leads to the coexpression of the CD4 receptor on the cell surface (18, 36). Recently, several groups provided evidence that, while HIVinfected CD8 precursors from the thymus rarely reach the periphery, the majority of circulating infected CD8 lymphocytes acquired HIV through expression of CD4 during activation (7,12). HIV-infected CD8 ϩ T-cell precursors have been suggested to be depleted intrathymically.…”

HIV-1 Nef Disrupts Intracellular Trafficking of Major Histocompatibility Complex Class I, CD4, CD8, and CD28 by Distinct Pathways That Share Common Elements

“…Significantly, a small population of CD4 ϩ CD8 ϩ T lymphocytes circulates in peripheral blood (9,30,64,65,97), and the frequency of these double-positive cells increases in response to infection with a number of viruses, including HIV (42, 52, 59). Additionally, these cells have been reported to be susceptible to infection by HIV (6,20,40,41,50,92,96). While the role of CD4 ϩ CD8 ϩ double-positive cells is not entirely clear, they are known to exhibit cytolytic activity as well as the antigen-dependent secretion of gamma interferon (IFN-␥) and IL-2.…”

Durable Human Memory T Cells Quantifiable by Cultured Enzyme-Linked Immunospot Assays Are Induced by Heterologous Prime Boost Immunization and Correlate with Protection against Malaria

“…that there is de novo expression of CD4 on CD8 cells after activation and in HIV-positive individuals, 0.7-3.3% of CD8 ϩ T cells are double positive and most of these cells are in the memory subset (28,29). A population of CD4 ϩ CD8 ϩ double positive T cells has been identified as effector memory cells, is shown to control viral replication in hepatitis C virus-infected individuals and is commonly found as memory populations in other species (30,31).…”