Monoclonal antibodies to the common gamma-chain as cytokine receptor antagonists in vivo: effect on intrathymic and intestinal intraepithelial T lymphocyte development.
Mice lacking a functional gamma c subunit of cytokine receptors exhibit profound defects in the development of multiple lymphoid lineages. To investigate the role of gamma c-dependent cytokines in T cell development, the phenotype of developing T cells was compared in interleukin (IL)-7Ralpha-deficient mice and anti-gamma c mAb-treated chimeric mice reconstituted with adult bone marrow cells or subsets of pro-T cells. These studies indicate that gamma 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 gamma 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-7Ralpha-deficient mice indicates that the IL-7/IL-7R system is critical only for the development of TCR gammadelta+ IEL. However, the inhibitory activity of the anti-deltac mAb in the chimeric mouse model suggests that additional gamma cutilizing cytokines regulate the development of the remaining subsets of IEL.
Duke Scholars
Altmetric Attention Stats
Dimensions Citation Stats
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Thymus Gland
- T-Lymphocytes
- Recombinant Proteins
- Receptors, Interleukin-17
- Receptors, Interleukin
- Receptors, Cytokine
- Mice, Inbred C57BL
- Mice
- Intestines
- Interleukin-7
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Thymus Gland
- T-Lymphocytes
- Recombinant Proteins
- Receptors, Interleukin-17
- Receptors, Interleukin
- Receptors, Cytokine
- Mice, Inbred C57BL
- Mice
- Intestines
- Interleukin-7