Naive, Effector and Memory CD8 T-cell Trafficking: Parallels and Distinctions

Nolz, Jeffrey C.; Starbeck-Miller, Gabriel R.; Harty, John T.

doi:10.2217/imt.11.100

Cited by 127 publications

(107 citation statements)

References 85 publications

Supporting

Mentioning

103

Contrasting

Order By: Relevance

“…T M cells enter the cell cycle earlier and proliferate faster than T N cells after activation (3)(4)(5). Because T M cells are different from T N cells in their ability to migrate to peripheral tissues (30)(31)(32), these experiments do not exclude the possibility that T M cells respond more quickly because they encounter Ag before T N cells. Consistent with previous studies (3,4,33), we show here that T M cells are intrinsically different as they proliferate faster and make more cytokine after activation in vitro.…”

Section: Discussionmentioning

confidence: 99%

CD8 memory T cells have a bioenergetic advantage that underlies their rapid recall ability

Windt

O’Sullivan

Everts

et al. 2013

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

441

440

View full text Add to dashboard Cite

A characteristic of memory T (T M ) cells is their ability to mount faster and stronger responses to reinfection than naïve T (T N ) cells do in response to an initial infection. However, the mechanisms that allow this rapid recall are not completely understood. We found that CD8 T M cells have more mitochondrial mass than CD8 T N cells and, that upon activation, the resulting secondary effector T (T E ) cells proliferate more quickly, produce more cytokines, and maintain greater ATP levels than primary effector T cells. We also found that after activation, T M cells increase oxidative phosphorylation and aerobic glycolysis and sustain this increase to a greater extent than T N cells, suggesting that greater mitochondrial mass in T M cells not only promotes oxidative capacity, but also glycolytic capacity. We show that mitochondrial ATP is essential for the rapid induction of glycolysis in response to activation and the initiation of proliferation of both T N and T M cells. We also found that fatty acid oxidation is needed for T M cells to rapidly respond upon restimulation. Finally, we show that dissociation of the glycolysis enzyme hexokinase from mitochondria impairs proliferation and blocks the rapid induction of glycolysis upon T-cell receptor stimulation in T M cells. Our results demonstrate that greater mitochondrial mass endows T M cells with a bioenergetic advantage that underlies their ability to rapidly recall in response to reinfection. In addition, several intrinsic aspects of T M cells have been suggested to contribute to their ability to respond more efficiently, such as increased activity of proximal TCR signaling components, an "open" chromatin conformation of cytokine genes, and altered transcriptional profiles (1, 2, 5-9). However, whether bioenergetic differences contribute to this process is not clear.Resting cells like T N and T M cells interchangeably use glucose, amino acids, and lipids to fuel the tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OXPHOS) for ATP production (10-12). However, proliferating cells like activated T cells promote aerobic glycolysis, which supports cell growth, proliferation, and effector functions (13-16). Although T N and T M cells both have a similar metabolism, there are metabolic differences between these cells (17). T M cells from Listeria monocytogenes-infected mice have more mitochondria than T N cells, which is consistent with our finding that T M cells but not T N cells have considerable spare respiratory capacity (SRC) (17). Because SRC is important for cellular survival and function (17)(18)(19) and T M cells are characterized by their ability to respond vigorously to Ag reencounter (20), we investigated whether bioenergetic differences between T M and T N cells contribute to the ability of T M cells to rapidly recall in response to reinfection. We show here that T M cells have more mitochondria and ATP than T N cells and that, upon activation, secondary T E cells proliferate faster, produce cytokines more quickly, and maintain more ATP ...

show abstract

Section: Discussionmentioning

confidence: 99%

CD8 memory T cells have a bioenergetic advantage that underlies their rapid recall ability

Windt

O’Sullivan

Everts

et al. 2013

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

441

440

View full text Add to dashboard Cite

show abstract

“…Furthermore, immunity is made of a multifaceted set of integrated responses involving a dynamic interaction of thousands of molecules. It may be the case that cell-mediated immunity might be so complicated that there might be other mechanisms and factors involved (Nolz et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Human Embryonic Stem Cells - a Potential Vaccine for Ovarian Cancer

Zhang

Chen²,

Chang³

et al. 2012

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

show abstract

“…In the cancer setting, the presence of tumor-infiltrating lymphocytes (TIL) has been reported to correlate well with positive clinical outcomes (2-5). CD8 þ T cells are recruited from the circulation to the site of infection by a series of distinct processes, involving attachment/adhesion, rolling/tethering, chemotaxis, and extravasation (1,6). In general, T-cell trafficking to the tumor microenvironment is markedly reduced compared with an infectious disease setting due to both intrinsic and extrinsic factors (7).…”

Section: Trafficking Of Cd8mentioning

confidence: 99%

“…The binding of chemokine receptors causes activation of LFA-1 and newly expressed integrins, such as very late antigen 4 (VLA-4), which bind to ICAM-1 and vascular cell adhesion molecule 1 (VCAM-1), respectively, expressed on infected tissue, which enables adhesion. Further expression of chemokines by diseased tissue facilitates extravasation of T cells into the tissue to exert contact-dependent functions, resulting in resolution of the disease threat (1,6).…”

Section: Key Events In Lymphocyte Traffickingmentioning

confidence: 99%

Trafficking of T Cells into Tumors

2014

View full text Add to dashboard Cite

T cells are a crucial component of the immune response to infection and cancer. In addition to coordinating immunity in lymphoid tissue, T cells play a vital role at the disease site, which relies on their efficient and specific trafficking capabilities. The process of T-cell trafficking is highly dynamic, involving a series of distinct processes, which include rolling, adhesion, extravasation, and chemotaxis. Trafficking of T cells to the tumor microenvironment is critical for the success of cancer immunotherapies such as adoptive cellular transfer. Although this approach has achieved some remarkable responses in patients with advanced melanoma and hematologic malignancy, the success against solid cancers has been more moderate. One of the major challenges for adoptive immunotherapy is to be able to effectively target a higher frequency of T cells to the tumor microenvironment, overcoming hurdles associated with immunosuppression and aberrant vasculature. This review summarizes recent advances in our understanding of T-cell migration in solid cancer and immunotherapy based on the adoptive transfer of natural or genetically engineered tumor-specific T cells and discusses new strategies that may enhance the trafficking of these cells, leading to effective eradication of solid cancer and metastases. Cancer Res; 74(24); 7168-74. Ó2014 AACR.

show abstract

Naive, Effector and Memory CD8 T-cell Trafficking: Parallels and Distinctions

Cited by 127 publications

References 85 publications

CD8 memory T cells have a bioenergetic advantage that underlies their rapid recall ability

CD8 memory T cells have a bioenergetic advantage that underlies their rapid recall ability

Human Embryonic Stem Cells - a Potential Vaccine for Ovarian Cancer

Trafficking of T Cells into Tumors

Contact Info

Product

Resources

About