scholarly journals Coordinate Expression and Trans Presentation of Interleukin (IL)-15Rα and IL-15 Supports Natural Killer Cell and Memory CD8+ T Cell Homeostasis

2004 ◽  
Vol 200 (7) ◽  
pp. 825-834 ◽  
Author(s):  
Patrick R. Burkett ◽  
Rima Koka ◽  
Marcia Chien ◽  
Sophia Chai ◽  
David L. Boone ◽  
...  
Keyword(s):  
T Cells ◽  
Natural Killer ◽  
Cd8 T Cells ◽  
Killer Cell ◽  
Cellular Level ◽  
T Cell Homeostasis ◽  
Memory Cd8 T Cells ◽  
In Trans ◽  
Cd8 Memory T Cells

The high affinity interleukin (IL)-15 receptor, IL-15Rα, is essential for supporting lymphoid homeostasis. To assess whether IL-15Rα's role in vivo is to trans present IL-15, we generated mixed bone marrow chimera from IL-15Rα– and IL-2/15Rβ–deficient mice. We find that IL-15Rα–competent, IL-2/15Rβ–deficient cells are able to support IL-15Rα–deficient natural killer (NK) and memory CD8+ T cells, thus ruling out secondary signals on these cells and demonstrating that IL-15Rα–mediated presentation of IL-15 in trans is the primary mechanism by which IL-15Rα functions in vivo. Surprisingly, using IL-15– and IL-15Rα–deficient mixed chimera, we also find that IL-15 and IL-15Rα must be expressed by the same cells to present IL-15 in trans, indicating that IL-15Rα is required on a cellular level for the elaboration of IL-15. These studies indicate that IL-15Rα defines homeostatic niches for NK and memory CD8+ T cells by controlling both the production and the presentation of IL-15 in trans to NK and CD8+ memory T cells.

scholarly journals T Cell–Independent Interleukin 15rα Signals Are Required for Bystander Proliferation

2001 ◽  
Vol 194 (8) ◽  
pp. 1187-1194 ◽  
Author(s):  
James P. Lodolce ◽  
Patrick R. Burkett ◽  
David L. Boone ◽  
Marcia Chien ◽  
Averil Ma
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Bone Marrow Cells ◽  
Cd8 T Cell ◽  
Cell Receptor ◽  
Poly I:C ◽  
T Cell Homeostasis ◽  
Memory Cd8 T Cells

Cytokine driven or “bystander” proliferation of T cells occurs in vivo independently of major histocompatibility complex–T cell receptor interactions. This process may be important for supporting T cell homeostasis and facilitating T cell responses to microbial antigens, and may involve the cytokine interleukin (IL)-15. In this study, we find that IL-15Rα–deficient (IL-15Rα−/−) mice fail to undergo poly I:C or IL-15 driven bystander proliferation of CD8+ T cells. Surprisingly, IL-15Rα−/− CD8+ T cells proliferate in response to poly I:C when adoptively transferred into normal mice, and normal CD8+ T cells fail to proliferate in IL-15Rα−/− mice. Normal mice reconstituted with IL-15Rα−/− bone marrow cells also fail to exhibit bystander responses. Thus, CD8+ T cell independent IL-15Rα signals from radiation sensitive hematopoietic cells are likely required for bystander responses. Moreover, normal CD8+ T cells proliferate in IL-15Rα−/− mice after treatment with IL-15. Therefore, IL-15Rα signals may mediate a positive feedback loop involving the further physiological production of IL-15. These findings provide new insights into how IL-15Rα supports memory phenotype CD8+ T cell proliferation, and suggest novel mechanisms by which memory CD8+ T cells are maintained in vivo.

Paradoxic inhibition of human natural interferon-producing cells by the activating receptor NKp44

Blood ◽  
2005 ◽  
Vol 106 (6) ◽  
pp. 2076-2082 ◽  
Author(s):  
Anja Fuchs ◽  
Marina Cella ◽  
Takayuki Kondo ◽  
Marco Colonna
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Nk Cell ◽  
Close Contact ◽  
Killer Cell ◽  
Adaptor Protein ◽  
Interferon Α ◽  
Memory Cd8 T Cells ◽  
Activating Receptor

Abstract Natural killer (NK) cell-mediated cytotoxicity is triggered by multiple activating receptors associated with the signaling adaptor protein DNAX activation protein 12/killer cell-activating receptor-associated protein (DAP12/KARAP). Here, we show that one of these receptors, NKp44, is present on a subset of natural interferon-producing cells (IPCs) in tonsils. NKp44 expression can also be induced on blood IPCs after in vitro culture with interleukin 3 (IL-3). Crosslinking of NKp44 does not trigger IPC-mediated cytotoxicity but, paradoxically, inhibits interferon α (IFN-α) production by IPCs in response to cytosine-phosphate-guanosine (CpG) oligonucleotides. We find that IPCs in tonsils are in close contact with CD8+ T cells and demonstrate that a subset of memory CD8+ T cells produces IL-3. Therefore, IL-3-mediated induction of NKp44 on IPCs may be an important component of the ongoing crosstalk between the innate and adaptive immune response that allows memory CD8+ T cells to control the IPC response to virus. (Blood. 2005;106: 2076-2082)

scholarly journals p53 Hinders CRISPR/Cas9-Mediated Targeted Gene Disruption in Memory CD8 T Cells In Vivo

2020 ◽  
Vol 205 (8) ◽  
pp. 2222-2230
Author(s):  
Samarchith P. Kurup ◽  
Steven J. Moioffer ◽  
Lecia L. Pewe ◽  
John T. Harty
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Gene Disruption ◽  
Memory Cd8 T Cells ◽  
Targeted Gene Disruption

scholarly journals Human memory CD8 T cell effector potential is epigenetically preserved during in vivo homeostasis

2017 ◽  
Vol 214 (6) ◽  
pp. 1593-1606 ◽  
Author(s):  
Hossam A. Abdelsamed ◽  
Ardiana Moustaki ◽  
Yiping Fan ◽  
Pranay Dogra ◽  
Hazem E. Ghoneim ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cd8 T Cell ◽  
Human Memory ◽  
Memory Cd8 T Cells ◽  
Memory Cd8 T Cell ◽  
Cell Effector

Antigen-independent homeostasis of memory CD8 T cells is vital for sustaining long-lived T cell–mediated immunity. In this study, we report that maintenance of human memory CD8 T cell effector potential during in vitro and in vivo homeostatic proliferation is coupled to preservation of acquired DNA methylation programs. Whole-genome bisulfite sequencing of primary human naive, short-lived effector memory (TEM), and longer-lived central memory (TCM) and stem cell memory (TSCM) CD8 T cells identified effector molecules with demethylated promoters and poised for expression. Effector-loci demethylation was heritably preserved during IL-7– and IL-15–mediated in vitro cell proliferation. Conversely, cytokine-driven proliferation of TCM and TSCM memory cells resulted in phenotypic conversion into TEM cells and was coupled to increased methylation of the CCR7 and Tcf7 loci. Furthermore, haploidentical donor memory CD8 T cells undergoing in vivo proliferation in lymphodepleted recipients also maintained their effector-associated demethylated status but acquired TEM-associated programs. These data demonstrate that effector-associated epigenetic programs are preserved during cytokine-driven subset interconversion of human memory CD8 T cells.

Response of naïve and memory CD8+ T cells to antigen stimulation in vivo

10.1038/76907 ◽  
2000 ◽  
Vol 1 (1) ◽  
pp. 47-53 ◽  
Author(s):  
Henrique Veiga-Fernandes ◽  
Ulrich Walter ◽  
Christine Bourgeois ◽  
Angela McLean ◽  
Benedita Rocha
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Memory Cd8 T Cells ◽  
Antigen Stimulation

scholarly journals PD-1 is a regulator of virus-specific CD8+ T cell survival in HIV infection

2006 ◽  
Vol 203 (10) ◽  
pp. 2281-2292 ◽  
Author(s):  
Constantinos Petrovas ◽  
Joseph P. Casazza ◽  
Jason M. Brenchley ◽  
David A. Price ◽  
Emma Gostick ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cd8 T Cell ◽  
Antigen Specificity ◽  
Chronic Infections ◽  
Human Virus ◽  
Memory Cd8 T Cells ◽  
Persistent Virus

Here, we report on the expression of programmed death (PD)-1 on human virus-specific CD8+ T cells and the effect of manipulating signaling through PD-1 on the survival, proliferation, and cytokine function of these cells. PD-1 expression was found to be low on naive CD8+ T cells and increased on memory CD8+ T cells according to antigen specificity. Memory CD8+ T cells specific for poorly controlled chronic persistent virus (HIV) more frequently expressed PD-1 than memory CD8+ T cells specific for well-controlled persistent virus (cytomegalovirus) or acute (vaccinia) viruses. PD-1 expression was independent of maturational markers on memory CD8+ T cells and was not directly associated with an inability to produce cytokines. Importantly, the level of PD-1 surface expression was the primary determinant of apoptosis sensitivity of virus-specific CD8+ T cells. Manipulation of PD-1 led to changes in the ability of the cells to survive and expand, which, over several days, affected the number of cells expressing cytokines. Therefore, PD-1 is a major regulator of apoptosis that can impact the frequency of antiviral T cells in chronic infections such as HIV, and could be manipulated to improve HIV-specific CD8+ T cell numbers, but possibly not all functions in vivo.

NKp80 defines and stimulates a reactive subset of CD8 T cells

Blood ◽  
2009 ◽  
Vol 113 (2) ◽  
pp. 358-369 ◽  
Author(s):  
Sabrina Kuttruff ◽  
Sven Koch ◽  
Alexandra Kelp ◽  
Graham Pawelec ◽  
Hans-Georg Rammensee ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Natural Killer ◽  
Cd8 T Cells ◽  
Cell Subset ◽  
T Cell Responses ◽  
Effector Memory ◽  
Memory Cd8 T Cells ◽  
Cell Responses ◽  
Natural Killer Gene Complex

Abstract NKp80, an activating homodimeric C-type lectin-like receptor (CTLR), is expressed on essentially all human natural killer (NK) cells and stimulates their cytotoxicity and cytokine release. Recently, we demonstrated that the ligand for NKp80 is the myeloid-specific CTLR activation-induced C-type lectin (AICL), which is encoded in the natural killer gene complex (NKC) adjacent to NKp80. Here, we show that NKp80 also is expressed on a minor fraction of human CD8 T cells that exhibit a high responsiveness and an effector memory phenotype. Gene expression profiling and flow cytometric analyses revealed that this NKp80+ T-cell subset is characterized by the coexpression of other NK receptors and increased levels of cytotoxic effector molecules and adhesion molecules mediating access to sites of inflammation. NKp80 ligation augmented CD3-stimulated degranulation and interferon (IFN)γ secretion by effector memory T cells. Furthermore, engagement of NKp80 by AICL-expressing transfectants or macrophages markedly enhanced CD8 T-cell responses in alloreactive settings. Collectively, our data demonstrate that NKp80 is expressed on a highly responsive subset of effector memory CD8 T cells with an inflammatory NK-like phenotype and promotes T-cell responses toward AICL-expressing cells. Hence, NKp80 may enable effector memory CD8 T cells to interact functionally with cells of myeloid origin at sites of inflammation.

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