Comparative Analysis of Cytotoxic T Lymphocytes in Lymph Nodes and Peripheral Blood of Simian Immunodeficiency Virus-Infected Rhesus Monkeys

Kuroda, Marcelo J.; Schmitz, Jörn E.; Charini, William A.; Nickerson, Christine E.; Lord, Carol I.; Forman, Meryl A.; Letvin, Norman L.

doi:10.1128/jvi.73.2.1573-1579.1999

Cited by 76 publications

(30 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The infection in rhesus macaques is artificial, and large inoculating virus doses have to be used to ensure infection. The challenge virus is more aggressive and the kinetics of infection and disease progression are faster than in humans (52, 54). Nevertheless, in Mamu A*01-positive animals there was an early Tat-specific CD8 T cell response that selected escape mutations quickly while virus load was falling, and this was followed by a response to the stable Gag CM9 epitope which escapes rarely and slowly (52).…”

Section: Discussionmentioning

confidence: 99%

The first T cell response to transmitted/founder virus contributes to the control of acute viremia in HIV-1 infection

Goonetilleke

Liu

Salazar-Gonzalez

et al. 2009

Journal of Experimental Medicine

574

791

View full text Add to dashboard Cite

Identification of the transmitted/founder virus makes possible, for the first time, a genome-wide analysis of host immune responses against the infecting HIV-1 proteome. A complete dissection was made of the primary HIV-1–specific T cell response induced in three acutely infected patients. Cellular assays, together with new algorithms which identify sites of positive selection in the virus genome, showed that primary HIV-1–specific T cells rapidly select escape mutations concurrent with falling virus load in acute infection. Kinetic analysis and mathematical modeling of virus immune escape showed that the contribution of CD8 T cell–mediated killing of productively infected cells was earlier and much greater than previously recognized and that it contributed to the initial decline of plasma virus in acute infection. After virus escape, these first T cell responses often rapidly waned, leaving or being succeeded by T cell responses to epitopes which escaped more slowly or were invariant. These latter responses are likely to be important in maintaining the already established virus set point. In addition to mutations selected by T cells, there were other selected regions that accrued mutations more gradually but were not associated with a T cell response. These included clusters of mutations in envelope that were targeted by NAbs, a few isolated sites that reverted to the consensus sequence, and bystander mutations in linkage with T cell–driven escape.

show abstract

Section: Discussionmentioning

confidence: 99%

The first T cell response to transmitted/founder virus contributes to the control of acute viremia in HIV-1 infection

Goonetilleke

Liu

Salazar-Gonzalez

et al. 2009

Journal of Experimental Medicine

574

791

View full text Add to dashboard Cite

show abstract

“…In models where macaques have been infected with SIV, it has been possible to perform detailed experimental studies of acute disease and the kinetics of infection and distribution of CTL [47,48]. Further discussion of the SIV model is outwith the scope of this review, but readers may wish to refer to recent papers from the groups of Letvin and Watkins [47±52].…”

Section: Hivmentioning

confidence: 99%

Studies of human antiviral CD8+ lymphocytes using class I peptide tetramers

Lechner

Cuero

Καντζάνου

et al. 2001

Reviews in Medical Virology

View full text Add to dashboard Cite

Understanding the interactions between a host and a pathogen relies crucially on quantitative measurements of immune responses. Until recently, measurements of the levels of cellular immune responses, i.e. those mediated by CD4+ and CD8+ T lymphocytes have depended largely on culture in vitro and subsequent measurement of specific functions (such as cytolysis). More recently, new technologies based around tetrameric class I peptide complexes (tetramers) have allowed immunologists to measure CD8+ T lymphocyte levels directly ex vivo and independently of function. Since CD8+ lymphocytes play a key role in a number of important human viral infections, these tools have yielded useful insights into the dynamics, phenotype and function of human antiviral lymphocyte populations. In this review we describe some of the basic aspects of the biology of virus-specific CD8+ lymphocytes, and the current methods available to detect them. The use of tetramers has, in just four years, transformed our understanding of the immune responses against HIV, HTLV-1, HBV, HCV, CMV and EBV, and holds promise in a number of areas where quantitative analysis of the antiviral response in terms of both number and function is critical.

show abstract

“…Among the most powerful of these is the tetramer technology, which utilizes soluble class I major histocompatibility complex (MHC)-peptide tetrameric complexes, permitting the direct visualization and quantification of antigen specific T cells immediately ex vivo [2]. Using this technique, several studies have quantified virus-specific cells in the peripheral blood, lymph nodes [9], liver [11], and intestine [12] of SIV-infected macaques. More recently, the emergence and kinetics of SIV-specific CTL in the intestinal tract in primary (first 63 days) SIV infection of three SIV-infected macaques were compared [16].…”

Section: Introductionmentioning

confidence: 99%

Dynamics of Simian immunodeficiency virus‐specific cytotoxic T‐cell responses in tissues

Veazey

Lifson

Schmitz

et al. 2003

J of Medical Primatology

Self Cite

View full text Add to dashboard Cite

Although the dynamics of human immunodeficiency virus and Simian immunodeficiency virus (SIV)-specific cytotoxic T cells (CTLs) have been well documented in the blood, little is known regarding CTL development in other tissues. In this study, seven Mamu-A*01+ macaques were inoculated with SIVmac. Two macaques were killed at 21 days of infection, and SIV gag p11C tetramer responses were measured in the blood, axillary and mesenteric lymph nodes, spleen, bone marrow, and thymus. Three with clinical signs of disease were killed and similarly examined. Four macaques were followed throughout disease progression, and intestinal biopsies and blood were examined at regular time points after inoculation. In animals followed prospectively, peak early tetramer responses were detected in the blood (3.9-19% of CD3+ CD8+ T cells) between day 14-21 post-inoculation (p.i.). After day 49, tetramer responses in the blood diminished and remained relatively stable through day 200, ranging from 0.7-6.5% of CD3+ CD8+ T cells. In contrast, tetramer-positive T cells increased in the intestine in later stages of infection (100-200 days p.i.) in all four infected animals (peak values from 5.3 to 28.8%). Percentages of tetramer-positive cells were consistently higher in the intestine than in the blood in all four animals after day 100. In animals with acquired immunodeficiency syndrome, percentages of CTL in tissues were variable, but were consistently higher in the intestine and spleen compared with blood. These data suggest that while high CTL responses develop at a similar rate, and magnitude in both peripheral and mucosal lymphoid tissues in primary SIV infection, mucosal CTL responses may predominate later in the course of the disease.

show abstract

Comparative Analysis of Cytotoxic T Lymphocytes in Lymph Nodes and Peripheral Blood of Simian Immunodeficiency Virus-Infected Rhesus Monkeys

Cited by 76 publications

References 35 publications

The first T cell response to transmitted/founder virus contributes to the control of acute viremia in HIV-1 infection

The first T cell response to transmitted/founder virus contributes to the control of acute viremia in HIV-1 infection

Studies of human antiviral CD8+ lymphocytes using class I peptide tetramers

Dynamics of Simian immunodeficiency virus‐specific cytotoxic T‐cell responses in tissues

Contact Info

Product

Resources

About