scholarly journals Interleukin-7 promotes human regulatory T cell development at the CD4+ CD8+ double-positive thymocyte stage

2016 ◽  
Vol 100 (3) ◽  
pp. 491-498 ◽  
Author(s):  
Anni Tuulasvaara ◽  
Reetta Vanhanen ◽  
Hanna-Mari Baldauf ◽  
Juha Puntila ◽  
T. Petteri Arstila
Keyword(s):  
T Cell ◽  
Regulatory T Cell ◽  
T Cell Development ◽  
Cell Development ◽  
Double Positive ◽  
Interleukin 7 ◽  
Double Positive Thymocyte

scholarly journals Cutaneous lymphoproliferation and lymphomas in interleukin 7 transgenic mice.

1993 ◽  
Vol 177 (2) ◽  
pp. 305-316 ◽  
Author(s):  
B E Rich ◽  
J Campos-Torres ◽  
R I Tepper ◽  
R W Moreadith ◽  
P Leder
Keyword(s):  
T Cell ◽  
Transgenic Mice ◽  
T Cell Development ◽  
Living Organism ◽  
Cell Development ◽  
Lymphoid Tissues ◽  
Double Positive ◽  
Interleukin 7 ◽  
T Cell Lymphomas ◽  
Skin Homing

To investigate the role of interleukin 7 (IL-7) in the development of the lymphoid system, we have generated two lines of transgenic mice carrying an IL-7 cDNA fused to an immunoglobulin heavy chain promoter and enhancer. This transgene is expressed in the bone marrow, lymph nodes, spleen, thymus, and skin provoking a perturbation of T cell development characterized by a marked reduction of CD4+ CD8+ (double-positive) thymocytes. Quite unexpectedly, however, both lines also develop a progressive cutaneous disorder involving a dermal lymphoid infiltrate that results in progressive alopecia, hyperkeratosis, and exfoliation. Although the infiltrate is primarily composed of T lineage cells, its development is not impeded in the athymic nu/nu background. Furthermore, the phenotype can be transmitted horizontally by transplanting lymphoid tissues or skin to syngeneic wild-type mice. Thus, the phenotype is conveyed by skin-homing, mobile cells (presumably the infiltrating lymphocytes) in a cell-autonomous fashion. In addition to the skin phenotype, this transgene also provokes the development of a lymphoproliferative disorder that induces B and T cell lymphomas within the first 4 mo of life. These findings suggest potential physiologic actions of IL-7 in T cell development and in cutaneous immunity. They also demonstrate that IL-7 can act as an oncogene in the living organism.

scholarly journals The role of the Runx transcription factors in thymocyte differentiation and in homeostasis of naive T cells

2007 ◽  
Vol 204 (8) ◽  
pp. 1945-1957 ◽  
Author(s):  
Takeshi Egawa ◽  
Robert E. Tillman ◽  
Yoshinori Naoe ◽  
Ichiro Taniuchi ◽  
Dan R. Littman
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Development ◽  
Cell Development ◽  
Cytotoxic T Cell ◽  
Thymocyte Development ◽  
Double Positive ◽  
Interleukin 7 ◽  
Genes Encoding ◽  
Single Positive

Members of the Runx family of transcriptional regulators are required for the appropriate expression of CD4 and CD8 at discrete stages of T cell development. The roles of these factors in other aspects of T cell development are unknown. We used a strategy to conditionally inactivate the genes encoding Runx1 or Runx3 at different stages of thymocyte development, demonstrating that Runx1 regulates the transitions of developing thymocytes from the CD4−CD8− double-negative stage to the CD4+CD8+ double-positive (DP) stage and from the DP stage to the mature single-positive stage. Runx1 and Runx3 deficiencies caused marked reductions in mature thymocytes and T cells of the CD4+ helper and CD8+ cytotoxic T cell lineages, respectively. Runx1-deficient CD4+ T cells had markedly reduced expression of the interleukin 7 receptor and exhibited shorter survival. In addition, inactivation of both Runx1 and Runx3 at the DP stages resulted in a severe block in development of CD8+ mature thymocytes. These results indicate that Runx proteins have important roles at multiple stages of T cell development and in the homeostasis of mature T cells.

scholarly journals CD45-null transgenic mice reveal a positive regulatory role for CD45 in early thymocyte development, in the selection of CD4+CD8+ thymocytes, and B cell maturation.

1996 ◽  
Vol 183 (4) ◽  
pp. 1707-1718 ◽  
Author(s):  
K F Byth ◽  
L A Conroy ◽  
S Howlett ◽  
A J Smith ◽  
J May ◽  
...  
Keyword(s):  
Signal Transduction ◽  
T Cell ◽  
B Cells ◽  
Transgenic Mice ◽  
B Cell ◽  
T Cell Development ◽  
Cell Development ◽  
Cross Linking ◽  
Thymocyte Development ◽  
Double Positive

The CD45 transmembrane glycoprotein has been shown to be a protein phosphotyrosine phosphatase and to be important in signal transduction in T and B lymphocytes. We have employed gene targeting to create a strain of transgenic mice that completely lacks expression of all isoforms of CD45. The spleens from CD45-null mice contain approximately twice the number of B cells and one fifth the number of T cells found in normal controls. The increase in B cell numbers is due to the specific expansion of two B cell subpopulations that express high levels of immunoglobulin (IgM) staining. T cell development is significantly inhibited in CD45-null animals at two distinct stages. The efficiency of the development of CD4-CD8- thymocytes into CD4+ CD8+ thymocytes is reduced by twofold, subsequently the frequency of successful maturation of the double positive population into mature, single positive thymocytes is reduced by a further four- to fivefold. In addition, we demonstrate that CD45-null thymocytes are severely impaired in their apoptotic response to cross-linking signals via T cell receptor (TCR) in fetal thymic organ culture. In contrast, apoptosis can be induced normally in CD45-null thymocytes by non-TCR-mediated signals. Since both positive and negative selection require signals through the TCR complex, these findings suggest that CD45 is an important regulator of signal transduction via the TCR complex at multiple stages of T cell development. CD45 is absolutely required for the transmission of mitogenic signals via IgM and IgD. By contrast, CD45-null B cells proliferate as well as wild-type cells to CD40-mediated signals. The proliferation of B cells in response to CD38 cross-linking is significantly reduced but not abolished by the CD45-null mutation. We conclude that CD45 is not required at any stage during the generation of mature peripheral B cells, however its loss reveals a previously unrecognized role for CD45 in the regulation of certain subpopulations of B cells.

scholarly journals Mitochondrial and cytosolic roles of PINK1 shape induced regulatory T-cell development and function

2013 ◽  
Vol 43 (12) ◽  
pp. 3355-3360 ◽  
Author(s):  
Gavin I. Ellis ◽  
Lianteng Zhi ◽  
Ravi Akundi ◽  
Hansruedi Büeler ◽  
Francesc Marti
Keyword(s):  
T Cell ◽  
Regulatory T Cell ◽  
T Cell Development ◽  
Cell Development ◽  
And Function

Single-Cell Transcriptomics Reveals Discrete Steps in Regulatory T Cell Development in the Human Thymus

2021 ◽  
pp. ji2100506
Author(s):  
Florencia Morgana ◽  
Rianne Opstelten ◽  
Manon C. Slot ◽  
Andrew M. Scott ◽  
René A. W. van Lier ◽  
...  
Keyword(s):  
T Cell ◽  
Single Cell ◽  
Regulatory T Cell ◽  
T Cell Development ◽  
Cell Development ◽  
Human Thymus

Altered thymocyte and T cell development in neonatal mice with hyperoxia-induced lung injury

2018 ◽  
Vol 46 (4) ◽  
pp. 441-449
Author(s):  
Sowmya Angusamy ◽  
Tamer Mansour ◽  
Mohammed Abdulmageed ◽  
Rachel Han ◽  
Brian C. Schutte ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lung Injury ◽  
T Cell Development ◽  
Adaptive Immune System ◽  
Cell Development ◽  
Thymocyte Development ◽  
Double Positive ◽  
Neonatal Mice ◽  
Single Positive

Abstract Background: The adaptive immune system of neonates is relatively underdeveloped. The thymus is an essential organ for adaptive T cell development and might be affected during the natural course of oxygen induced lung injury. The effect of prolonged hyperoxia on the thymus, thymocyte and T cell development, and its proliferation has not been studied extensively. Methods: Neonatal mice were exposed to 85% oxygen (hyperoxia) or room air (normoxia) up to 28 days. Flow cytometry using surface markers were used to assay for thymocyte development and proliferation. Results: Mice exposed to prolonged hyperoxia had evidence of lung injury associated alveolar simplification, a significantly lower mean weight, smaller thymic size, lower mean thymocyte count and higher percentage of apoptotic thymocytes. T cells subpopulation in the thymus showed a significant reduction in the count and proliferation of double positive and double negative T cells. There was a significant reduction in the count and proliferation of single positive CD4+ and CD8+ T cells. Conclusions: Prolonged hyperoxia in neonatal mice adversely affected thymic size, thymocyte count and altered the distribution of T cells sub-populations. These results are consistent with the hypothesis that prolonged hyperoxia causes defective development of T cells in the thymus.

scholarly journals Unexpected Regulatory Role of CCR9 in Regulatory T Cell Development

PLoS ONE ◽  
2015 ◽  
Vol 10 (7) ◽  
pp. e0134100 ◽  
Author(s):  
Heather L. Evans-Marin ◽  
Anthony T. Cao ◽  
Suxia Yao ◽  
Feidi Chen ◽  
Chong He ◽  
...  
Keyword(s):  
T Cell ◽  
Regulatory T Cell ◽  
T Cell Development ◽  
Cell Development ◽  
Regulatory Role
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