Antigenic stimulation by BCG vaccine as an in vivo driving force for SIV replication and dissemination

Cheynier, Rémi; Gratton, Sophie; Halloran, Matilda; Stahmer, Ingrid; Letvin, Norman L.; Wain‐Hobson, Simon

doi:10.1038/nm0498-421

Cited by 49 publications

(50 citation statements)

References 35 publications

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“…Because DTH reactions are mediated inter alia by activated memory CD4 T cells, this reaction should provide a milieu conducive to SIV replication (9,10). The DTH reaction was studied by RT-PCR and ISH of 5-m dermal sections (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The absence of DNA contamination was confirmed by CD3␥ chain PCR as described (2). cDNAs were generated and then amplified by nested RT-PCR as described (9). Primers were as follows:…”

Section: Methodsmentioning

confidence: 99%

“…Amplification of TCR ␤ sequences was performed on 1 g DNA aliquots as described (9). DNA was used for specific amplification with SJ␤1.3-30, SJ␤1.6-30, SJ␤2.3-30, and SJ␤2.7-100 primers in combination with primers for the 10 major TCRBV segments.…”

Section: Methodsmentioning

confidence: 99%

“…However, these cells can be recruited to sites of immune responses and activated, thus resulting in proviral transcription (9,10) and leading to strong founder effects (11). In this way, HIV or SIV enters into the center of an immunological reaction, in a manner described as a ''Trojan horse'' mechanism (12,13).…”

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confidence: 99%

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The infiltration kinetics of simian immunodeficiency virus-specific T cells drawn to sites of high antigenic stimulation determines localin vivoviral escape

Blancou

Chenciner

Cumont

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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Despite vigorous cell-mediated immune responses to human and simian immunodeficiency viruses (HIV͞SIV) the immune system is unable to clear latently infected resting T cells. These infected cells are reactivated by antigenic stimulation, leading to viral replication. By using the SIV͞macaque model of HIV pathogenesis, the dynamics of T cell infiltration into delayed type hypersensitivity sites specific for the purified protein derivative of bacillus Calmette-Gué rin have been studied. Early viral mRNA synthesis coincided with the infiltration of antigen-specific T cells. When the infiltration of anti-SIV-specific T cells was rapid compared with the kinetics of viral assembly, the sites were sterilized before the transition to late viral mRNA synthesis occurred. When their infiltration was slow, ephemeral foci of replication were identified. These findings were paralleled by plasma viremia; low viremia coincided with rapid sterilization of the delayed type hypersensitivity sites, whereas high load was found in association with local replication and delayed sterilization. These data suggest that although effective local control of SIV is possible once antiviral T lymphocytes have arrived on site, the slower deployment of these T cells may allow the virus to escape and thus to reseed the pool of memory T cells.H uman and simian immunodeficiency virus (HIV͞SIV) replication is particularly apparent in the immunocompetent structures of secondary lymphoid organs such as spleen, lymph nodes, or Peyer's patches, where antigenic stimulation is intense. These structures are extensively infiltrated by CD8 ϩ T cells (1), which strongly control viremia at a local level (ref. 2; unpublished data). Thus, depletion of macaque CD8 cells by treatment with monoclonal antibodies in vivo resulted in massive SIV expansion as evidenced by a 10-to 100-fold increase in plasma viremia (3). Yet, despite strong CD8 T cell responses, viremia and the proportion of infected cells increase remorselessly over time, indicating that the virus is able to overcome antiviral immunity. Many explanations accounting for the progression to AIDS have been proffered, including the high-level replication in sanctuaries (4) or mutation within epitopes (5-7).The persistence of the virus can be partly attributed to the presence of latently infected CD4 T cells, in which the provirus, being transcriptionally silent, is invisible to specific immunity (8). However, these cells can be recruited to sites of immune responses and activated, thus resulting in proviral transcription (9, 10) and leading to strong founder effects (11). In this way, HIV or SIV enters into the center of an immunological reaction, in a manner described as a ''Trojan horse '' mechanism (12, 13). After activation of latently infected, antigen-specific T cells, there is a window of Ϸ10 h between the onset of early protein synthesis and the shedding of virus (14). Some of these proteins are catabolized to peptides and presented in the context of cell surface MHC class I molecules. These comple...

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Section: Resultsmentioning

confidence: 99%

“…The absence of DNA contamination was confirmed by CD3␥ chain PCR as described (2). cDNAs were generated and then amplified by nested RT-PCR as described (9). Primers were as follows:…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

The infiltration kinetics of simian immunodeficiency virus-specific T cells drawn to sites of high antigenic stimulation determines localin vivoviral escape

Blancou

Chenciner

Cumont

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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“…Thermokinetic principles such as GC content and certain nucleotide repeats were also considered as factors in determining the position and length of a primer. Similarly, three sets of 13 reverse Jβ primers were designed based on genomic DNA sequences of corresponding monkey Jβ genes (Cheynier et al, 1998). Thirteen external JR primers (ext.Jβ) were designed based on intron DNA sequences flanked at 3′to each of TCR Jβ regions (11), whereas middle and internal Jβ primers (mid.Jβ and int.Jβ) were complementary in sequences to the regions within the Jβ segments.…”

Section: Isolation Of Tcr Vdj Dna From Small Numbers Of Formaldehyde-mentioning

confidence: 99%

Combined megaplex TCR isolation and SMART-based real-time quantitation methods for quantitating antigen-specific T cell clones in mycobacterial infection

Qiu

Shen

et al. 2006

Journal of Immunological Methods

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Despite recent advances in measuring cellular immune responses, the quantitation of antigen-specific T cell clones in infections or diseases remains challenging. Here, we employed combined megaplex TCR isolation and SMART-based real-time quantitation methods to quantitate numerous antigenspecific T cell clones using limited amounts of specimens. The megaplex TCR isolation covered the repertoire comprised of recombinants from 24 Vβ families and 13 Jβ segments, and allowed us to isolate TCR VDJ clonotypic sequences from one or many PPD-specific IFNγ-producing T cells that were purified by flow cytometry sorting. The SMART amplification technique was then validated for its capacity to proportionally enrich cellular TCR mRNA/cDNA for real-time quantitation of large numbers of T cell clones. SMART amplified cDNA was shown to maintain relative expression levels of TCR genes when compared to unamplified cDNA. While the SMART-based real-time quantitative PCR conferred a detection limit of 10 −5 to 10 −6 antigen-specific T cells, the clonotypic primers specifically amplified and quantitated the target clone TCR but discriminated other clones that differed by ≥2 bases in the DJ regions. Furthermore, the combined megaplex TCR isolation and SMART-based real-time quantiation methods allowed us to quantitate large numbers of PPD-specific IFNγ-producing T cell clones using as few as 2×10 6 PBMC collected weekly after mycobacterial infection. This assay system may be useful for studies of antigen-specific T cell clones in tumors, autoimmune and infectious diseases.

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CD4+ T-Cells Are Required for the Establishment of Maedi-visna Virus Infection in Macrophages but Not Dendritic Cells in Vivo

et al. 1999

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The role of CD4(+) lymphocytes in the establishment of lentivirus infection in macrophages has been studied in an in vivo system of lentivirus infection where CD4(+) lymphocytes are not the targets for infection. Using the non-T-cell-tropic lentivirus, maedi-visna virus (MVV), in CD4-depleted sheep, we have found that CD4(+) T cells were required for MVV infection in macrophages but not dendritic cells. CD4-depleted sheep had significantly lower levels of MVV-infected cells in lymph nodes and efferent lymph after MVV challenge in the drainage area of the lymph node. Due to the absence of virus in combination with the lack of CD4(+) T helper cells, virus-specific immune responses were reduced. There was delayed induction of cytotoxic T cell precursors, a marked reduction in virus-specific in vitro proliferative responses, and a delay in the appearance of MVV-specific antibodies. By contrast, CD4 depletion had no effect on the establishment of MVV infection in afferent lymph dendritic cells migrating from the skin infection site to the lymph node.

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Antigenic stimulation by BCG vaccine as an in vivo driving force for SIV replication and dissemination

Cited by 49 publications

References 35 publications

The infiltration kinetics of simian immunodeficiency virus-specific T cells drawn to sites of high antigenic stimulation determines localin vivoviral escape

The infiltration kinetics of simian immunodeficiency virus-specific T cells drawn to sites of high antigenic stimulation determines localin vivoviral escape

Combined megaplex TCR isolation and SMART-based real-time quantitation methods for quantitating antigen-specific T cell clones in mycobacterial infection

CD4+ T-Cells Are Required for the Establishment of Maedi-visna Virus Infection in Macrophages but Not Dendritic Cells in Vivo

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