scholarly journals Highly efficient CD4+ T cell targeting and genetic recombination using engineered CD4+ cell-homing mRNA-LNP

2021 ◽  
Author(s):  
István Tombácz ◽  
Dorottya Laczkó ◽  
Hamna Shahnawaz ◽  
Hiromi Muramatsu ◽  
Ambika Natesan ◽  
...  
Keyword(s):  
T Cell ◽  
Genetic Recombination ◽  
Cd4 T Cell ◽  
Cell Targeting ◽  
Cell Homing ◽  
Highly Efficient ◽  
Cd4 Cell

IL-6 enhances CD4 cell motility by sustaining mitochondrial Ca2+ through the noncanonical STAT3 pathway

2021 ◽  
Vol 118 (37) ◽  
pp. e2103444118
Author(s):  
Felipe Valença-Pereira ◽  
Qian Fang ◽  
Isabelle J. Marié ◽  
Emily L. Giddings ◽  
Karen A. Fortner ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Motility ◽  
Cd4 T Cells ◽  
Cell Function ◽  
Inflammatory Diseases ◽  
Cd4 T Cell ◽  
Noncanonical Pathway ◽  
Cd4 Cell ◽  
Intrinsic Effect

Interleukin 6 (IL-6) is known to regulate the CD4 T cell function by inducing gene expression of a number of cytokines through activation of Stat3 transcription factor. Here, we reveal that IL-6 strengthens the mechanics of CD4 T cells. The presence of IL-6 during activation of mouse and human CD4 T cells enhances their motility (random walk and exploratory spread), resulting in an increase in travel distance and higher velocity. This is an intrinsic effect of IL-6 on CD4 T-cell fitness that involves an increase in mitochondrial Ca2+. Although Stat3 transcriptional activity is dispensable for this process, IL-6 uses mitochondrial Stat3 to enhance mitochondrial Ca2+-mediated motility of CD4 T cells. Thus, through a noncanonical pathway, IL-6 can improve competitive fitness of CD4 T cells by facilitating cell motility. These results could lead to alternative therapeutic strategies for inflammatory diseases in which IL-6 plays a pathogenic role.

scholarly journals Altered CD4+ T cell homing to the gut impairs mucosal immune reconstitution in treated HIV-infected individuals

2012 ◽  
Vol 122 (1) ◽  
pp. 62-69 ◽  
Author(s):  
Maud Mavigner ◽  
Michelle Cazabat ◽  
Martine Dubois ◽  
Fatima-Ezzahra L’Faqihi ◽  
Mary Requena ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Reconstitution ◽  
Cd4 T Cell ◽  
Cell Homing ◽  
T Cell Homing

scholarly journals VLA-4 mediates CD3-dependent CD4+ T cell activation via the CS1 alternatively spliced domain of fibronectin.

1990 ◽  
Vol 172 (4) ◽  
pp. 1185-1192 ◽  
Author(s):  
Y Nojima ◽  
M J Humphries ◽  
A P Mould ◽  
A Komoriya ◽  
K M Yamada ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cd4 T Cell ◽  
T Cell Proliferation ◽  
Cd4 Cells ◽  
Alternatively Spliced ◽  
Cd4 Cell ◽  
Native Plasma

We previously showed that fibronectin (FN) synergized with anti-CD3 in induction of CD4+ T cell proliferation, and that VLA-5 acted as a functional FN receptor in a serum-free culture system. In the present study, we showed that VLA-4 is also involved in this CD3-dependent CD4 cell activation through its interaction with the alternatively spliced CS1 domain of FN. When highly purified CD4 cells were cultured on plates coated with anti-CD3 plus synthetic CS1 peptide-IgG conjugate, significant proliferation could be observed. Neither CS1 alone nor anti-CD3 alone induced this activation. This proliferation was completely blocked by anti-VLA beta 1 (4B4) and anti-VLA-4 (8F2), while anti-VLA-5 (monoclonal antibody [mAb] 16 and 2H6) had no effect. These data indicate that VLA-4 mediates CD3-dependent CD4 cell proliferation via the CS1 domain of FN. Anti-VLA-4 also partially (10-40%) inhibited CD4 cell proliferation induced by native FN plus anti-CD3, implying that the CS1 domain is active in the native plasma FN. However, this native FN-dependent proliferation was entirely abolished by addition of anti-VLA-5 alone. Moreover, when native FN-coated plates were pretreated with anti-FN (mAb 333), which blocks RGDS sites but not CS1 sites, no CD4 cell activation could be observed. These results strongly suggest that CD4 cell activation induced by plasma FN/anti-CD3 may be dependent on both VLA4/CS1 and VLA5/RGDS interactions, although the latter interaction may be required for function of the former.

scholarly journals A peripheral CD4+ T cell precursor for naive, memory, and regulatory T cells

2010 ◽  
Vol 207 (13) ◽  
pp. 2883-2894 ◽  
Author(s):  
Chunfang Zhao ◽  
Joanna D. Davies
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Cell Receptor ◽  
Cd4 T Cell ◽  
Interleukin 7 ◽  
Cell Pool ◽  
Tcr Repertoire ◽  
B Cell Leukemia ◽  
Cd4 Cell

Mechanisms that control the size of the T cell pool, the ratio between naive cells and memory cells, the number and frequency of regulatory T cells, and T cell receptor (TCR) diversity are necessary to maintain immune integrity and avoid disease. We have previously shown that a subset of naive CD4+ T cells, defined by the expression on their surface of a very low density of CD44 (CD44v.low cells), can inhibit wasting and wasting-associated lymphopenia in mice with cancer. In this study, we further investigate the properties of CD44v.low cells and show that they are significantly more efficient than the remaining naive (CD44low or CD44int) and memory CD4+ cell subsets in reconstituting the overall size of the CD4+ T cell pool, creating a T cell pool with a diverse TCR repertoire, generating regulatory T cells that express forkhead box P3 (FoxP3), and promoting homeostatic equilibrium between naive, memory, and Foxp3+ regulatory T cell numbers. T cell population reconstitution by CD44v.low cells is thymus independent. Compared with CD44int cells, a higher percentage of CD44v.low cells express B cell leukemia/lymphoma 2, interleukin-7 receptor, and CD5. The data support a key role for CD4+ CD44v.low cells as peripheral precursors that maintain the integrity of the CD4+ T cell pool.

The impact of diabetes on CD4 recovery in persons with HIV in an urban clinic in the United States

2017 ◽  
Vol 29 (1) ◽  
pp. 63-71 ◽  
Author(s):  
Julie A Zuniga ◽  
Kirk A Easley ◽  
Neeta Shenvi ◽  
Minh L Nguyen ◽  
Marcia Holstad
Keyword(s):  
African American ◽  
T Cell ◽  
Cell Count ◽  
African American Women ◽  
Cd4 T Cell ◽  
Cd4 Cell Count ◽  
Cell Counts ◽  
Cd4 Cell ◽  
The Impact ◽  
Cd4 T Cell Count

The purpose of this study was to exam the impact of type 2 diabetes mellitus (T2DM) on CD4 cell count trends in adults with HIV. In a longitudinal retrospective study in an urban primary care HIV clinic in the southeastern United States from 2010 to 2012, patients with HIV medical charts were audited to obtain their CD4 cell count, diabetes status, weight, and demographic information. Rates of increase of CD4 T cell count (i.e. slopes) were obtained using a linear mixed-effects model. Most of the HIV–T2DM cohort (n = 262) and HIV-only cohort (n = 2399) were African American (76%) and male (77%). The CD4 T cell counts were consistently higher in the HIV–T2DM cohort ( p < .0001). The mean rate of CD4 T cell count increase (mean ± SE) was 63 ± 9 cells/µl/year in HIV–T2DM African American women and 28 ± 7 cells/µl/year in HIV–T2DM African American men ( p = 0.003). In the multivariable slope analysis, the CD4 T cell count increase was significantly faster for HIV–T2DM African American women than for all other patients (mean difference = 30/cells/µl/year, 95% CI: 13–47; p < 0.001). Gender, race/ethnicity, and the diagnosis of diabetes influenced the recovery of CD4 cell counts.

Endogenous estrogens, through estrogen receptor α, constrain autoimmune inflammation in female mice by limiting CD4+ T-cell homing into the CNS

2010 ◽  
Vol 40 (12) ◽  
pp. 3489-3498 ◽  
Author(s):  
Karine Lélu ◽  
Laurent Delpy ◽  
Virginie Robert ◽  
Eliane Foulon ◽  
Sophie Laffont ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
T Cell ◽  
Estrogen Receptor Α ◽  
Cd4 T Cell ◽  
Cell Homing ◽  
Female Mice ◽  
Autoimmune Inflammation ◽  
T Cell Homing
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