Unexpected prolonged presentation of influenza antigens promotes CD4 T cell memory generation

Jelley-Gibbs, Dawn M.; Brown, Deborah M.; Dibble, John; Haynes, Laura; Eaton, Sheri M.; Swain, Susan L.

doi:10.1084/jem.20050227

Cited by 234 publications

(320 citation statements)

References 55 publications

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“…Recent reports from us and others show that antigen is present in LN of mice for at least 2 months after intranasal influenza virus infection (14,55). Interestingly, in this case, antigen was detectable only in the LN draining the respiratory tract, namely, the cervical and mediastinal LN.…”

Section: Discussionmentioning

confidence: 59%

“…However, there may also exist infections previously categorized as acute in which viral antigen and perhaps viral genetic material are present for protracted time periods. Recently, such a scenario has been described following intranasal infection of mice with the segmented negative-stranded RNA influenza virus, a member of the Orthomyxoviridae family (14,55). Thus, influenza virus nucleoprotein (NP)-derived antigenic peptides are present in the lung-draining LN for at least 60 days postinfection.…”

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confidence: 99%

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Persistent Antigen Presentation after Acute Vesicular Stomatitis Virus Infection

Turner

Cauley

Khanna

et al. 2007

J Virol

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Long-term antigen expression is believed to play an important role in modulation of T-cell responses to chronic virus infections. However, recent studies suggest that immune responses may occur late after apparently acute infections. We have now analyzed the CD8 T-cell response to vesicular stomatitis virus (VSV), which is thought to cause to an infection characterized by rapid virus clearance by innate and adaptive immune system components. Unexpectedly, virus-encoded antigen was detectable more than 6 weeks after intranasal VSV infection in both draining and nondraining lymph nodes by adoptively transferred CD8 T cells. Infection with Listeria monocytogenes expressing the same antigen did not result in prolonged antigen presentation. Weeks after VSV infection, discrete T-cell clustering with dendritic cells within the lymph node was observed after transfer of antigen-specific CD8 T cells. Moreover, memory CD8 T cells as defined by phenotype and function were generated from naïve CD8 T cells entering the response late after infection. These findings suggested that protracted antigen presentation after an apparently acute virus infection may contribute to an ongoing antiviral immune response.

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Section: Discussionmentioning

confidence: 59%

mentioning

confidence: 99%

Persistent Antigen Presentation after Acute Vesicular Stomatitis Virus Infection

Turner

Cauley

Khanna

et al. 2007

J Virol

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“…Highly differentiated CD4 1 CD28 À T cells, found in RA and linked with disease severity, are potent producers of effector cytokines, and display an important cytotoxic potential. Factors controlling the magnitude and quality of CD4 1 T-cell responses have previously been described, including the amount and duration of antigen [37][38][39] type of antigen presentation [40] as well as the surrounding cytokine milieu [41]. Here, we have analyzed the multifunctional profile of CD4 1 CD28 À T cells from RA patients.…”

Section: Discussionmentioning

confidence: 99%

Activating NK‐cell receptors co‐stimulate CD4⁺CD28⁻ T cells in patients with rheumatoid arthritis

et al. 2010

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Effector T‐cell responses can be modulated by competing positive or negative signals transduced by NK‐cell receptors (NKR). In the CD4+ T‐cell population, the expression of NKR is primarily found in the CD4+CD28− T‐cell subset, also known as CD28null T cells. These T cells are frequently found in rheumatoid arthritis (RA) and other inflammatory disorders, suggesting that signaling through NKR may play a role in the autoimmune reaction. Here we aimed to dissect the phenotype and function of NKR‐expressing CD4+CD28− T cells in patients with RA. By analyzing a broad array of NKR on CD4+CD28− T cells we found a significant expression of the co‐activating receptors 2B4 (CD244), DNAM‐1 (CD226), and CRACC. Pair‐wise ligations of 2B4 with DNAM‐1 and/or NKG2D lead to increased effector functions of primary CD4+CD28− T cells to suboptimal levels of anti‐CD3 stimulation. Using multi‐parameter flow cytometry, we demonstrate that such co‐ligation led to an increased magnitude in overall responsiveness without changing qualitative aspects of the response. Altogether these results demonstrate a pattern of additive effects in NKR‐mediated functional modulation of CD4+CD28− T cells in RA. This may have consequences for the inflammatory responses imposed by these cells, thus influencing disease manifestations.

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“…Long‐term maintenance of antigen has been demonstrated for follicular dendritic cells108 and even in the absence of any detectable pathogen after viral challenge, antigen can apparently persist in amounts sufficient to stimulate adoptively transferred, naive T cells 109…”

Section: The Lifestyle Of Circulating Memory T Lymphocytesmentioning

confidence: 99%

Immunological memories of the bone marrow

Chang

Tokoyoda

Radbruch

2018

Immunological Reviews

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SummaryMemory for antigens once encountered is a hallmark of the immune system of vertebrates, providing us with an immunity adapted to pathogens of our environment. Despite its fundamental relevance, the cells and genes representing immunological memory are still poorly understood. Here we discuss the concept of a circulating, proliferating, and ubiquitous population of effector lymphocytes vs concepts of resting and dormant populations of dedicated memory lymphocytes, distinct from effector lymphocytes and residing in defined tissues, particularly in barrier tissues and in the bone marrow. The lifestyle of memory plasma cells of the bone marrow may serve as a paradigm, showing that persistence of memory lymphocytes is not defined by intrinsic “half‐lives”, but rather conditional on distinct survival signals provided by dedicated niches. These niches are organized by individual mesenchymal stromal cells. They define the capacity of immunological memory and regulate its homeostasis.

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Unexpected prolonged presentation of influenza antigens promotes CD4 T cell memory generation

Cited by 234 publications

References 55 publications

Persistent Antigen Presentation after Acute Vesicular Stomatitis Virus Infection

Persistent Antigen Presentation after Acute Vesicular Stomatitis Virus Infection

Activating NK‐cell receptors co‐stimulate CD4⁺CD28⁻ T cells in patients with rheumatoid arthritis

Immunological memories of the bone marrow

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Unexpected prolonged presentation of influenza antigens promotes CD4 T cell memory generation

Cited by 234 publications

References 55 publications

Persistent Antigen Presentation after Acute Vesicular Stomatitis Virus Infection

Persistent Antigen Presentation after Acute Vesicular Stomatitis Virus Infection

Activating NK‐cell receptors co‐stimulate CD4+CD28− T cells in patients with rheumatoid arthritis

Immunological memories of the bone marrow

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Product

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Activating NK‐cell receptors co‐stimulate CD4⁺CD28⁻ T cells in patients with rheumatoid arthritis