Identifying the Target Cell in Primary Simian Immunodeficiency Virus (SIV) Infection: Highly Activated Memory CD4⁺T Cells Are Rapidly Eliminated in Early SIV Infection In Vivo

Abstract

It has recently been shown that rapid and profound CD4؉ T-cell depletion occurs almost exclusively within the intestinal tract of simian immunodeficiency virus (SIV)-infected macaques within days of infection. Here we demonstrate (by three-and four-color flow cytometry) that this depletion is specific to a definable subset of CD4 ؉ T cells, namely, those having both a highly and/or acutely activated (CD69 ؉ CD38 ؉ HLA-DR ؉ ) and memory (CD45RA ؊ Leu8 ؊ ) phenotype. Moreover, we demonstrate that this subset of helper T cells is found primarily within the intestinal lamina propria. Viral tropism for this particular cell type (which has been previously suggested by various studies in vitro) could explain why profound CD4 ؉ T-cell depletion occurs in the intestine and not in peripheral lymphoid tissues in early SIV infection. Furthermore, we demonstrate that an acute loss of this specific subset of activated memory CD4 ؉ T cells may also be detected in peripheral blood and lymph nodes in early SIV infection. However, since this particular cell type is present in such small numbers in circulation, its loss does not significantly affect total CD4 ؉ T cell counts. This finding suggests that SIV and, presumably, human immunodeficiency virus specifically infect, replicate in, and eliminate definable subsets of CD4 ؉ T cells in vivo.

New bis(thiosemicarbazonate) gold(III) complexes inhibit HIV replication at cytostatic concentrations: Potential for incorporation into virostatic cocktails

“…Geneva, June 1998, abstract 287/12235) that used an optimal cytostatic dose of HU in combination with anti-viral agents such as didanosine showed superior efficacy over trial groups that did not incorporate it [13]. The explanation for this is that, when a compound suppresses the activity of CD4+ cells, it is likely that activated (antigen presenting) and bystander cells (which are mostly affected by HIV apoptosis [43] are reduced such that these cells are not primed for killing by HIV leading to an overall steady state that is beneficial to the host. Such treatment strategies are encouraged as first-line combinations to reduce the emergence of resistant strains and at a point when the patients are asymptomatic so as to avoid complications that could arise in advance disease [26].…”

Differential cross-reactivity of monoclonal antibody OPD4 (anti-CD45RO) in macaques

“…The ability to distinguish naïve and memory subsets in macaques led to the discovery that simian immunodeficiency virus rapidly and selectively infects and eliminates "memory" CD4+ T cells, particularly in mucosal tissues [1][2][3], findings that were recently confirmed in HIV-infected patients [4,5]. These findings have revolutionized our understanding of HIV pathogenesis by demonstrating that HIV *Corresponding author: RS Veazey, Tulane National Primate Research Center, 18703 Three Rivers Road, Covington, LA 70433, Phone (985) 871-6228, Fax (985) 871-6510, Email: rveazey@tulane.edu.…”

In vivo 1H MRS of brain injury and repair during acute SIV infection in the macaque model of neuroAIDS

“…Lymphocytes were isolated from blood and stained for flow cytometric analysis as previously described (20). Samples were immunoreacted with monoclonal antibodies against human CD4 (Ortho Diagnostics, Raritan, NJ), CD8 (Becton Dickinson, San Jose, CA), and anti-rhesus CD3 (courtesy of J. Wong, Massachusetts General Hospital) directly conjugated to either FITC (fluorescein isothiocyanate), PE (phycoerithrin), PerCP (peridinin chlorophyll protein), or APC (allophycocyanin).…”