CD4+ T Cell Priming Accelerates the Clearance of Sendai Virus in Mice, but Has a Negative Effect on CD8+ T Cell Memory

Zhong, Weimin; Marshall, Dana; Coleclough, Christopher; Woodland, David L.

doi:10.4049/jimmunol.164.6.3274

Cited by 40 publications

(34 citation statements)

References 48 publications

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“…A complete understanding of the cellular responses to M. tuberculosis will require knowledge of the T cell responses to many different Ags. Indeed, if a large proportion of the T cells recruited to the lung are M. tuberculosis specific, our data indicate that T cells that recognize many different Ags are involved in the response, because only 2% of the population recognized ESAT-6 [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] . Information regarding the full spectrum of Ags recognized will be critical for the evaluation of different vaccination strategies, because candidate vaccines might vary in their abilities to elicit responses to particular protective Ags.…”

Section: Discussionmentioning

confidence: 99%

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Persistence and Turnover of Antigen-Specific CD4 T Cells During Chronic Tuberculosis Infection in the Mouse

Winslow

Roberts

Blackman

et al. 2003

The Journal of Immunology

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CD4 T cells are critical for resistance to Mycobacterium tuberculosis infection, but how effective T cell responses are maintained during chronic infection is not well understood. To address this question we examined the CD4 T cell response to a peptide from ESAT-6 during tuberculosis infection in the mouse. The ESAT-61–20/IAb-specific CD4 T cell response in the lungs, mediastinal lymph nodes, and spleen reached maxima 3–4 wk postinfection, when the bacteria came under the control of the immune response. Once chronic infection was established, the relative frequencies of Ag-specific CD4 T cells were maintained at nearly constant levels for at least 160 days. ESAT-61–20/IAb-specific CD4 T cells that responded in vitro expressed activation markers characteristic of chronically activated effector cells and used a limited Vβ repertoire that was clonally stable in vivo for at least 12 wk. 5-Bromo-2-deoxyuridine incorporation studies indicated a relatively high rate of cell division among both total CD4 and ESAT-61–20/IAb-specific CD4 T cells during acute infection, but the degree of 5-bromo-2-deoxyuridine incorporation by both the CD4 T cells and the Ag-specific cells declined at least 3-fold during chronic infection. The data indicate that the peripheral ESAT-61–20/IAb-specific CD4 T cell response to M. tuberculosis is characterized during the acute phase of infection by a period of extensive proliferation, but once bacterial control is achieved, this is followed during chronic infection by an extended containment phase that is associated with a persistent response of activated, yet more slowly proliferating, T cells.

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Section: Discussionmentioning

confidence: 99%

“…Lung T cells were stimulated in vitro with ESAT-6 [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] , and BrdU and IFN-␥ were measured simultaneously as described above. Only 11% of the ESAT-6 1-20 /IA b -specific CD4 T cells incorporated BrdU on day 125 (Fig.…”

Section: Turnover Of Ag-specific T Cellsmentioning

confidence: 99%

Persistence and Turnover of Antigen-Specific CD4 T Cells During Chronic Tuberculosis Infection in the Mouse

Winslow

Roberts

Blackman

et al. 2003

The Journal of Immunology

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“…In addition to providing B and T cell help, peptide-primed CD4 ϩ T cells can enhance viral clearance by an Ab-independent mechanism that is mediated in part by IFN-␥ (3,4). Interestingly, a recent study has shown that CD4 ϩ memory cells in lymphoid tissues are relatively unstable and decline progressively following the resolution of a viral infection (5).…”

Section: D4mentioning

confidence: 99%

“…These data have important implications for vaccination, because priming CD4 ϩ T cells with peptides can reduce the numbers of CD8 ϩ memory cells generated during viral infection (3,4), in essence replacing relatively stable CD8…”

Section: Cells the Numbers Of Virus-specific Cd4mentioning

confidence: 99%

Cutting Edge: Virus-Specific CD4+ Memory T Cells in Nonlymphoid Tissues Express a Highly Activated Phenotype

Cauley

Cookenham

Miller

et al. 2002

The Journal of Immunology

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Recent studies have shown that CD4+ memory T cells persist in nonlymphoid organs following infections. However, the development and phenotype of these peripheral memory cells are poorly defined. In this study, multimerized MHC-Ig fusion proteins, with a covalently attached peptide sequence from the Sendai virus hemagglutinin/neuraminidase gene, have been used to identify virus-specific CD4+ T cells during Sendai virus infection and the establishment of peripheral CD4+ memory populations in the lungs. We show declining frequencies of virus-specific CD4+ T cells in the lungs over the course of ∼3 mo after infection. Like peripheral CD8+ T cells, the CD4+ have an acutely activated phenotype, suggesting that a high level of differentiation is required to reach the airways and persist as memory cells. Differences in CD25 and CD11a expression indicate that the CD4+ cells from the lung airways and parenchyma are distinct memory populations.

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“…[27][28][29] Despite the potential complexity of antiviral T-cell responses, the recognition of virus both in mouse models and in humans is often highly focused on a small number of epitopes, making peptide-induced tolerance a realistic possibility. [30][31][32] Immunological tolerance may act through a number of different mechanisms, including deletion of reactive clones, anergy through incomplete or altered signalling and regulation by regulatory T cells. Here we evaluate the impact of inducing intranasal tolerance to the CD4 and CD8 immunodominant T-cell epitopes of SeV on gene expression following repeated administration to the airways.…”

Section: Introductionmentioning

confidence: 99%

Effect of tolerance induction to immunodominant T-cell epitopes of Sendai virus on gene expression following repeat administration to lung

et al. 2005

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Sendai virus (SeV) is able to transfect airway epithelial cells efficiently in vivo. However, as with other viral vectors, repeated administration leads to reduced gene expression. We have investigated the impact of inducing immunological tolerance to immunodominant T-cell epitopes on gene expression following repeated administration. Immunodominant CD4 and CD8 T-cell peptide epitopes of SeV were administered to C57BL/6 mice intranasally 10 days before the first virus administration with transmission-incompetent F-protein-deleted DF/SeV-GFP. At 21 days after the first virus administration, mice were again transfected with DF/SeV. To avoid interference of anti-GFP antibodies, the second transfection was carried out with DF/SeV-lacZ.At 2 days after the final transfection lung b-galactosidase expression, T-cell proliferation and antibody responses were measured. A state of 'split tolerance' was achieved with reduced T-cell proliferation, but no impact on antiviral antibody production. There was no enhancement of expression on repeat administration; instead, T-cell tolerance was, paradoxically, associated with a more profound extinction of viral expression. Multiple immune mechanisms operate to eradicate viruses from the lung, and these findings indicate that impeding the adaptive T-cell response to the immunodominant viral epitope is not sufficient to prevent the process.

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CD4+ T Cell Priming Accelerates the Clearance of Sendai Virus in Mice, but Has a Negative Effect on CD8+ T Cell Memory

Cited by 40 publications

References 48 publications

Persistence and Turnover of Antigen-Specific CD4 T Cells During Chronic Tuberculosis Infection in the Mouse

Persistence and Turnover of Antigen-Specific CD4 T Cells During Chronic Tuberculosis Infection in the Mouse

Cutting Edge: Virus-Specific CD4+ Memory T Cells in Nonlymphoid Tissues Express a Highly Activated Phenotype

Effect of tolerance induction to immunodominant T-cell epitopes of Sendai virus on gene expression following repeat administration to lung

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