scholarly journals mTOR modulates CD8+ T cell differentiation in mice with invasive pulmonary aspergillosis

2018 ◽  
Vol 13 (1) ◽  
pp. 129-136 ◽  
Author(s):  
Hao Wang ◽  
Yu Xiao ◽  
Longxiang Su ◽  
Na Cui ◽  
Dawei Liu
Keyword(s):  
Cell Proliferation ◽  
Cell Differentiation ◽  
T Cell ◽  
Invasive Pulmonary Aspergillosis ◽  
Mtor Pathway ◽  
Effector Memory ◽  
Pulmonary Aspergillosis ◽  
Tem Cell ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation

AbstractCD8+ T cells are a vital component of the adaptive immune system and important for eliminating intracellular pathogens. Notably, mTOR activity is associated with CD8+ T effector memory (Tem) cell differentiation in fungal infections. This study investigates the molecular mechanisms of CD8+ Tem cell proliferation and differentiation mediated by the mTOR pathway in immunosuppressed mice with invasive pulmonary aspergillosis (IPA). We first established the immunosuppressed IPA mouse model, then mice were subjected to rapamycin treatment daily or interleukin (IL)-12 treatment every other day. Lung tissues and blood samples were obtained seven days later. Aspergillus fumigatus was cultured from the lung tissue of mice inoculated with A. fumigatus spores. After IL-12 treatment, the expression of mTOR and its downstream signaling molecule S6 kinase, number of CD8+ Tem cells and interferon-γ expression were significantly increased, while they were significantly decreased after treatment with rapamycin. Additionally, IL-12 treatment induced T-bet but inhibited Eomesodermin expression, while the opposite was seen when the mTOR pathway was blocked by rapamycin. In conclusion, we found that the mTOR pathway induced CD8+ T cell proliferation and differentiation by regulating T-bet and Eomesodermin expression, which significantly influenced immune regulation during IPA and enhanced the immune response against fungal infection.

scholarly journals Costimulation by B7 Modulates Specificity of Cytotoxic T Lymphocytes: A Missing Link That Explains Some Bystander T Cell Activation

1997 ◽  
Vol 186 (10) ◽  
pp. 1787-1791 ◽  
Author(s):  
Pan Zheng ◽  
Yang Liu
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
Influenza Virus ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
T Cell Proliferation ◽  
Target Cells ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation

It has been proposed that some bystander T cell activation may in fact be due to T cell antigen receptor (TCR) cross-reactivity that is too low to be detected by the effector cytotoxic T lymphocyte (CTL). However, this hypothesis is not supported by direct evidence since no TCR ligand is known to induce T cell proliferation and differentiation without being recognized by the effector CTL. Here we report that transgenic T cells expressing a T cell receptor to influenza virus A/NT/68 nucleoprotein (NP) 366-374:Db complexes clonally expand and become effector CTLs in response to homologous peptides from either A/PR8/34 (H1N1), A/AA/60 (H2N2), or A/NT/68 (H3N2). However, the effector T cells induced by each of the three peptides kill target cells pulsed with NP peptides from the H3N2 and H2N2 viruses, but not from the H1N1 virus. Thus, NP366–374 from influenza virus H1N1 is the first TCR ligand that can induce T cell proliferation and differentiation without being recognized by CTLs. Since induction of T cell proliferation was mediated by antigen-presenting cells that express costimulatory molecules such as B7, we investigated if cytolysis of H1N1 NP peptide–pulsed targets can be restored by expressing B7-1 on the target cells. Our results revealed that this is the case. These data demonstrated that costimulatory molecule B7 modulates antigen specificity of CTLs, and provides a missing link that explains some of the bystander T cell activation.

scholarly journals Poplar bark lipids enhance mouse immunity by inducing T cell proliferation and differentiation

2020 ◽  
Vol 82 (8) ◽  
pp. 1187-1196
Author(s):  
Jinxiu TANG ◽  
Xiuli WEI ◽  
Youzhi LI ◽  
Linlin JIANG ◽  
Tao FENG ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cell ◽  
T Cell Proliferation ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation

Microenvironment of Apatite-Fiber Scaffold Affects Cell Proliferation and Resulting Cell Differentiation

2007 ◽  
Vol 361-363 ◽  
pp. 1075-1078
Author(s):  
Michiyo Honda ◽  
Shigeki Izumi ◽  
Nobuyuki Kanzawa ◽  
Takahide Tsuchiya ◽  
Mamoru Aizawa
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Extracellular Matrix ◽  
Cell Proliferation ◽  
Cell Differentiation ◽  
Bone Marrow Cells ◽  
Three Dimensional ◽  
Bone Marrow Stem Cells ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation

Appropriate culture conditions cause bone marrow stem cells to differentiate into multilineage cells such as adipocytes, chondrocytes, and osteoblasts. One key factor that regulates intercellular signaling and cell differentiation is the extracellular matrix microenvironment. The composition of the extracellular matrix influences cellular functions. In the present study, we investigated the effects of a microenvironment comprising a three-dimensional apatite-fiber scaffold (AFS) that has two kinds of pores (micro- and macro pores) on proliferation and subsequent differentiation of bone marrow stem cells. Morphologic observation revealed that osteoblastic cells in the AFS were distributed primarily in the same location on the fibrous scaffold and formed bridges within micro- and macro pores. We used molecular approaches to evaluate cell proliferation and differentiation in detail. Reverse transcription-polymerase chain reaction (RT-PCR) analysis showed that culturing bone marrow cells on AFS increases expression of osteocalcin (OC) mRNA compared with culture in a dish. Furthermore, cells cultured in AFS expressed type X collagen (Col X), which is a marker of hypertrophic cartilage. These data suggest that the three-dimensional microenvironment of AFS facilitates cell proliferation and differentiation, and promotes endochondral ossification of bone marrow cells.

Depletion in nuclear spermine during human spermatogenesis, a natural process of cell differentiation

1992 ◽  
Vol 263 (2) ◽  
pp. C343-C347 ◽  
Author(s):  
V. Quemener ◽  
Y. Blanchard ◽  
D. Lescoat ◽  
R. Havouis ◽  
J. P. Moulinoux
Keyword(s):  
Cell Proliferation ◽  
Cell Differentiation ◽  
Mammalian Cells ◽  
Gradient Centrifugation ◽  
Cell Nuclei ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Human Spermatogenesis

Polyamines (PA), polycations present in all mammalian cells, are essential for cell proliferation and differentiation. In vitro, PA are known to bind to DNA with a high affinity. In vivo, the intimate association of endogenous PA with highly condensed chromatin has been reported. During spermatogenesis, when processes of cell proliferation and differentiation take place, the potential role of polyamines has not been studied in depth. We report here the PA levels measured in human spermatogenic cell nuclei at different stages of differentiation. Cell populations (spermatocytes and round, elongating, or elongated spermatids) were obtained after submitting human testes to a trypsin-deoxyribonuclease digestion, then to a centrifugal elutriation and Percoll gradient centrifugation. A significant and progressive nuclear spermine level decrease was observed from primary spermatocytes to elongated spermatids. This release of spermine from nuclei was concomitant with three major events in mammalian spermiogenesis: the reduction of DNA transcription activity, the replacement of histone proteins by protamines, and the compaction of chromatin. This is the first report arguing a release of nuclear spermine during an in vivo physiological cell differentiation process.

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