Number of CD4+ and CD8+ T-cell CDR3 clonotypes expanding during acute infection of macaques with simian immunodeficiency virus

Bernardin, Flavien; Dandekar, Satya; Rompay, Koen K. A. Van; Delwart, Eric

doi:10.1016/j.virol.2004.01.022

Cited by 3 publications

(1 citation statement)

References 71 publications

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“…Tissue-specific clonotypes have been identified in chronic SIV infection [ 9 ] and clonotypic discrepancies between the peripheral blood and other anatomical sites, such as lymphoid tissue, have been observed in chronic HIV infection [ 30 ]. During acute infection, clonal expansion of CD8 + T cells typically peaks at 4 weeks post infection [ 31 ], occurring during a period of reduced cytotoxicity, subsequent to initial increases in SIV-specific CD8 + T cells numbers [ 7 ]. The presence of public clonotypes in acute infection is suspected to reflect their large numbers in the naïve pool, due to the likely generation of these public clonotypes by convergent recombination in which the same amino acid can be encoded by multiple nucleotide sequences [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Multiple modes of antigen exposure induce clonotypically diverse epitope-specific CD8+ T cells across multiple tissues in nonhuman primates

et al. 2022

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Antigen-specific CD8+ T cells play a key role in the host’s antiviral response. T cells recognize viral epitopes via the T cell receptor (TCR), which contains the complementarity-determining region-3 (CDR3), comprising the variable, diversity and joining regions of the TCRβ gene. During chronic simian immunodeficiency virus (SIV) infection of Asian macaque nonhuman primates, tissue-specific clonotypes are identifiable among SIV-specific CD8+ T cells. Here, we sought to determine level of antigen exposure responsible for the tissue-specific clonotypic structure. We examined whether the priming event and/or chronic antigen exposure is response for tissue-specific TCR repertoires. We evaluated the TCR repertoire of SIV-specific CD8+ T cells after acute antigen exposure following inoculation with a SIV DNA vaccine, longitudinally during the acute and chronic phases of SIV, and after administration of antiretrovirals (ARVs). Finally, we assessed the TCR repertoire of cytomegalovirus (CMV)-specific CD8+ T cells to establish if TCR tissue-specificity is shared among viruses that chronically replicate. TCR sequences unique to anatomical sites were identified after acute antigen exposure via vaccination and upon acute SIV infection. Tissue-specific clones also persisted into chronic infection and the clonotypic structure continued to evolve after ARV administration. Finally, tissue-specific clones were also observed in CMV-specific CD8+ T cells. Together, these data suggest that acute antigen priming is sufficient to induce tissue-specific clones and that this clonal hierarchy can persist when antigen loads are naturally or therapeutically reduced, providing mechanistic insight into tissue-residency.

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Section: Discussionmentioning

confidence: 99%

Multiple modes of antigen exposure induce clonotypically diverse epitope-specific CD8+ T cells across multiple tissues in nonhuman primates

et al. 2022

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Analysis of T-cell receptor BV gene sequences in cattle reveals extensive duplication within the BV9 and BV20 subgroups

et al. 2005

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We investigated the repertoire of functional T-cell receptor beta-chain variable genes (TRBV genes) in cattle by analysing the nucleotide sequences and predicted amino acid sequences of a set of cDNA clones isolated from lymph node T cells. Thirty-nine distinct TRBV sequences were identified, bringing the total number of recognised bovine TRBV gene segments to more than 40. Sixteen TRBV subgroups were defined based on their sequence homology to each other and to human TRBV genes. All of the main phylogenetic lineages of BV gene subgroups described in humans and mice were represented. Eight of the subgroups were found to contain more than one member. The most striking feature of the results was the large number of sequences (more than half of the sequenced clones) in the BV9 and BV20 subgroups, which were found to contain 12 and 8 distinct sequences, respectively. In contrast, the corresponding human TRBV subfamilies contain a single member. The results indicate that, as in humans, there has been extensive gene duplication within the TRBV locus during evolution. However, duplication of different BV subgroups in cattle has resulted in a TRBV gene repertoire distinct from that found in other species.

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CD8⁺-Cell-Mediated Suppression of Virulent Simian Immunodeficiency Virus during Tenofovir Treatment

Rompay

Singh

Pahar

et al. 2004

J Virol

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The ability of tenofovir to suppress viremia in simian immunodeficiency virus (SIV)-infected macaques for years despite the presence of virulent viral mutants with reduced in vitro susceptibility is unprecedented in this animal model. In vivo cell depletion experiments demonstrate that tenofovir's ability to suppress viremia during acute and chronic infection is significantly dependent on the presence of CD8 ؉ lymphocytes. Continuous tenofovir treatment was required to maintain low viremia. Although it is unclear whether this immunemediated suppression of viremia is linked to tenofovir's direct antiviral efficacy or is due to independent immunomodulatory effects, these studies prove the concept that antiviral immune responses can play a crucial role in suppressing viremia during anti-human immunodeficiency virus drug therapy.Although highly active antiretroviral therapy (HAART) regimens provide significant progress in the clinical management of human immunodeficiency virus (HIV) infection, their longterm use is often limited by problems such as incomplete virus suppression and drug resistance. To alleviate this problem, it is believed we need to invoke the help of the immune system to help limit virus replication and/or the virus-induced immune dysfunction.Immune responses, especially cell-mediated immune responses (CD4 ϩ -T-helper cells and CD8 ϩ T lymphocytes) are thought to play an important role in controlling virus replication and determining disease-free survival. Evidence for this comes from studies in untreated long-term nonprogressors (for a review, see reference 2). In addition, macaque data have shown conclusively that CD8 ϩ lymphocytes play an important role in limiting lentivirus replication because in vivo CD8ϩ -cell depletion of untreated macaques resulted in an increase in viremia (23,34,67).A number of dilemmas exist, however, for patients receiving HAART. HAART initiated during acute HIV infection can often preserve or increase antiviral immune responses, but episodes of transient viremia may be required to maintain these responses (54, 63). In contrast, when HAART is initiated during chronic HIV infection, HIV-specific immune responses are more difficult to restore (for a review, see reference 2).The goal of immunotherapeutic strategies is to augment these antiviral immune responses to prevent the emergence and/or the replication of drug-resistant mutants during HAART or to allow simplified regimens or periods without drug treatment. Although different approaches are investigated to stimulate antiviral immune responses (e.g., structured treatment interruptions, active immunizations, and cytokines), the results have been poor or success has been limited mainly to patients with acute infection with often transient results (2,3,25,63). Progress in this area may depend on a better understanding of the contribution of antiviral immune responses to the reduction of viremia during HAART and of the complex in vivo interactions of viral replication, drug resistance, immune responses, and drug pharmacok...

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Number of CD4+ and CD8+ T-cell CDR3 clonotypes expanding during acute infection of macaques with simian immunodeficiency virus

Cited by 3 publications

References 71 publications

Multiple modes of antigen exposure induce clonotypically diverse epitope-specific CD8+ T cells across multiple tissues in nonhuman primates

Multiple modes of antigen exposure induce clonotypically diverse epitope-specific CD8+ T cells across multiple tissues in nonhuman primates

Analysis of T-cell receptor BV gene sequences in cattle reveals extensive duplication within the BV9 and BV20 subgroups

CD8⁺-Cell-Mediated Suppression of Virulent Simian Immunodeficiency Virus during Tenofovir Treatment

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Number of CD4+ and CD8+ T-cell CDR3 clonotypes expanding during acute infection of macaques with simian immunodeficiency virus

Cited by 3 publications

References 71 publications

Multiple modes of antigen exposure induce clonotypically diverse epitope-specific CD8+ T cells across multiple tissues in nonhuman primates

Multiple modes of antigen exposure induce clonotypically diverse epitope-specific CD8+ T cells across multiple tissues in nonhuman primates

Analysis of T-cell receptor BV gene sequences in cattle reveals extensive duplication within the BV9 and BV20 subgroups

CD8+-Cell-Mediated Suppression of Virulent Simian Immunodeficiency Virus during Tenofovir Treatment

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CD8⁺-Cell-Mediated Suppression of Virulent Simian Immunodeficiency Virus during Tenofovir Treatment