Neuropilin-1 is a T cell memory checkpoint limiting long-term antitumor immunity

The cellular basis of immunological memory has been a debated issue. It is not clear whether CD8 T cell memory is maintained by long-lived cells or by specific or nonspecific restimulation. Here, we have approached the question from a different angle, asking whether the cellular interactions that are required to maintain memory are the same as those necessary to activate cytotoxic T lymphocytes. We studied the CD8 memory response to the male antigen H-Y in mice deficient in CD4 cells, or B cells and found that memory in these mice was virtually unimpaired. These results suggest that CD8 memory is CD4 independent and that there is no requirement for long term retention of immune complexes on follicular dendritic cells, nor for B cells as antigen-presenting cells.

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Long term persistence of T cell memory to HBsAg after hepatitis B vaccination

World Journal of Gastroenterology ◽

10.3748/wjg.v10.i2.260 ◽

2004 ◽

Vol 10 (2) ◽

pp. 260 ◽

Cited By ~ 27

Author(s):

Ru-Xiang Wang ◽

Greet J. Boland ◽

Jan van Hattum ◽

Gijsbert C. de Gast

Keyword(s):

T Cell ◽

Hepatitis B ◽

T Cell Memory ◽

Hepatitis B Vaccination ◽

Cell Memory

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Cholesterol-lowering Decreased mTOR Complex 2 Signaling and Enhanced Antitumor Immunity

10.1101/2021.01.29.21250381 ◽

2021 ◽

Author(s):

Yanping Wang ◽

Sungyong You ◽

Shengchen Su ◽

Austin Yeon ◽

Eric M. Lo ◽

...

Keyword(s):

T Cell ◽

Serum Cholesterol ◽

Antitumor Immunity ◽

Cd8 T Cell ◽

T Cell Memory ◽

Lymphocyte Function ◽

Dependent Manner ◽

Cell Memory ◽

Cholesterol Lowering ◽

Cd8 T Cell Memory

SummaryCholesterol-lowering interventions are employed widely and safely to reduce risk of cardiovascular disease. Cholesterol may have complex and opposing effects on immunity. We lowered serum cholesterol to clinically relevant levels in mice and evaluated the final adaptive immune response. Mice treated with oral ezetimibe exhibited enhanced antitumor immunity against syngeneic cancers in a CD8+ lymphocyte-dependent manner, produced immunity that was transferrable through lymphocytes, and enhanced central CD8+ T cell memory. In both mice and patients undergoing prostatectomy, lowering serum cholesterol inhibited mTORC2 signaling in lymphocytes and increased infiltration of CD8+ lymphocytes into prostate tumors. Lymphocyte-specific mTORC2 knockout mice demonstrated enhanced CD8+ lymphocyte function and antitumor capacity. In a prospective clinical trial, cholesterol-lowering intervention prior to prostatectomy decreased the proliferation of normal prostate and low-grade adenocarcinomas. Here, we show that lowering serum cholesterol may be an effective strategy to decrease signaling through mTORC2 and enhance antitumor CD8+ T cell memory.

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Quantitative Analysis of Long-Term Virus-Specific CD8+-T-Cell Memory in Mice Challenged with Unrelated Pathogens

Journal of Virology ◽

10.1128/jvi.77.14.7756-7763.2003 ◽

2003 ◽

Vol 77 (14) ◽

pp. 7756-7763 ◽

Cited By ~ 24

Author(s):

Haiyan Liu ◽

Samita Andreansky ◽

Gabriela Diaz ◽

Stephen J. Turner ◽

Dominik Wodarz ◽

...

Keyword(s):

Influenza Virus ◽

T Cell ◽

Influenza A Virus ◽

Influenza A ◽

Respiratory Infections ◽

T Cell Memory ◽

Cell Memory ◽

Immune Effector ◽

Memory Cytotoxic T Lymphocytes

ABSTRACT The consequences for the long-term maintenance of virus-specific CD8+-T-cell memory have been analyzed experimentally for sequential respiratory infections with readily eliminated (influenza virus) and persistent (gammaherpesvirus 68 [γHV68]) pathogens. Sampling a broad range of tissue sites established that the numbers of CD8+ T cells specific for the prominent influenza virus DbNP366 epitope were reduced by about half in mice that had been challenged 100 days previously with γHV68, though the prior presence of a large CD8+ DbNP366 + population caused no selective defect in the γHV68-specific CD8+ Kbp79+ response. Conversely, mice that had been primed and boosted to generate substantial γHV68-specific CD8+ Dbp56+ populations did not show any decrease in prevalence for this set of CD8+ memory cytotoxic T lymphocytes (CTL) at 200 days after respiratory exposure to an influenza A virus. However, in both experiments, the total magnitude of the CD8+-T-cell pool was significantly diminished in those that had been infected with γHV68 and the influenza A virus. The broader implications of these findings, especially under conditions of repeated exposure to unrelated pathogens, are explored with a mathematical model which emphasizes that the immune effector and memory “phenome” is a function of the overall infection experience of the individual.

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