Cytokine production and requirements during T-cell development

Zlotnik, Albert; Moore, Thomas A.

doi:10.1016/0952-7915(95)80005-0

Cited by 95 publications

(49 citation statements)

References 51 publications

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“…During the past several years, the advance of embryonic stem cell technology has made it possible to study the in vivo functions of cytokines utilizing mice with a targeted disruption of a given cytokine or cytokine receptor gene [74,75]. Recently, in order to confirm the role of TNF-␣ in LC migration and to examine which type of TNF receptor signaling is involved in such an event, we have utilized mutant mice deficient in TNF receptor I (p55) or II (p75).…”

Section: Studies Using Gene Knockout Micementioning

confidence: 99%

Role of cytokines in epidermal Langerhans cell migration

Wang

Amerio

Sauder

1999

Journal of Leukocyte Biology

151

107

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Section: Studies Using Gene Knockout Micementioning

confidence: 99%

Role of cytokines in epidermal Langerhans cell migration

Wang

Amerio

Sauder

1999

Journal of Leukocyte Biology

151

107

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“…Mouse thymic pro-T cell development has been defined in some detail and four phenotypic stages of increasing maturity have been described based on CD44 and CD25 expression [1][2][3][4]. Stage 1 (CD44 ϩ CD25 Ϫ ) pro-T cells maintain multi-lymphoid lineage potential.…”

Section: Introductionmentioning

confidence: 99%

Monoclonal antibodies to the common γ-chain as cytokine receptor antagonists in vivo: effect on intrathymic and intestinal intraepithelial T lymphocyte development

Malek

Levy²,

Adkins

et al. 1998

Journal of Leukocyte Biology

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Mice lacking a functional ␥c subunit of cytokine receptors exhibit profound defects in the development of multiple lymphoid lineages. To investigate the role of ␥c-dependent cytokines in T cell development, the phenotype of developing T cells was compared in interleukin (IL)-7R␣-deficient mice and anti-␥c mAb-treated chimeric mice reconstituted with adult bone marrow cells or subsets of pro-T cells. These studies indicate that ␥c contributes to T cell development at multiple stages of pro-T cell maturation and that IL-7/IL-7R is the primary cytokine for thymic-dependent T cell development. However, our data also implicate other ␥c-dependent cytokines during thymic T cell development. By contrast, substantial intestinal intraepithelial lymphocytes (IEL) development was observed in the intestinal intraepithelium in both types of mice. Analysis of IL-7R␣-deficient mice indicates that the IL-7/IL-7R system is critical only for the development of TCR ␥␦ ؉ IEL. However, the inhibitory activity of the anti-␥c mAb in the chimeric mouse model suggests that additional ␥c-utilizing cytokines regulate the development of the remaining subsets of IEL.

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“…The ␣␤ T cells are produced through a series of developmental steps involving survival, proliferation, and differentiation of these stem cell precursors driven by cell-cell interactions, growth factors, and cytokines provided by the thymic microenvironment (9,10). In the adult mouse thymus, the earliest precursors of the T cell pathway are within the population defined phenotypically as CD3 Ϫ CD4 low CD8 Ϫ (11).…”

mentioning

confidence: 99%

IL-7 and Not Stem Cell Factor Reverses Both the Increase in Apoptosis and the Decline in Thymopoiesis Seen in Aged Mice

Andrew

Aspinall

2001

The Journal of Immunology

129

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Thymic atrophy is an age-associated decline in commitment to the T cell lineage considered to be associated with defective TCR β-chain rearrangement. Both IL-7 and stem cell factor (SCF) have dominant roles at this stage of triple negative (TN) thymocyte development. Because there is no age-associated decrease in the number of CD44+CD25−CD3−CD4−CD8− cells, this study investigated whether alterations in apoptosis within the TN pathway accounted for diminishing thymocyte numbers with age. Here we show significant age-associated increases in apoptotic TN thymocytes, specifically within CD44+CD25+ and CD44−CD25+ subpopulations, known to be the location of TCR β-chain rearrangement. IL-7 added to TN cultures established from old mice significantly both reduces apoptosis and increases the percentage of live cells within CD44+CD25+ and CD44−CD25+ subpopulations after 24 h, with prosurvival effects remaining after 5 days. SCF failed to demonstrate prosurvival effects in old or young cultures, and IL-7 and SCF together did not improve upon IL-7 alone. IL-7R expression did not decline with age, ruling out the possibility that the age-associated increase in apoptosis was attributed to reduced IL-7R expression. Compared with PBS, treatment of old mice with IL-7 produced significant increases in live TN cells. By comparison, treatment with SCF failed to increase live TN numbers, and IL-7 and SCF together failed to significantly improve thymopoiesis above that shown by IL-7 alone. Thus, treatment with IL-7 alone can reverse the age-associated defect in TN thymocyte development revealed by in vitro studies to be located at the stages of TCR β-chain rearrangement.

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Cytokine production and requirements during T-cell development

Cited by 95 publications

References 51 publications

Role of cytokines in epidermal Langerhans cell migration

Role of cytokines in epidermal Langerhans cell migration

Monoclonal antibodies to the common γ-chain as cytokine receptor antagonists in vivo: effect on intrathymic and intestinal intraepithelial T lymphocyte development

IL-7 and Not Stem Cell Factor Reverses Both the Increase in Apoptosis and the Decline in Thymopoiesis Seen in Aged Mice

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