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.
Malek
T R
TR
Department of Microbiology and Immunology, University of Miami School of Medicine, Florida 33101, USA. tmalek@mednet.med.miami.edu
Levy
R B
RB
Adkins
B
B
He
Y W
YW
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D002678:Chimera; D016207:Cytokines / Q000502:physiology*; D004847:Epithelial Cells / Q000166:cytology; D005260:Female; D007142:Immunoglobulin gamma-Chains / Q000276:immunology*; D015851:Interleukin-7 / Q000502:physiology; D007422:Intestines / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D018121:Receptors, Cytokine / Q000037:antagonists & inhibitors*; D018123:Receptors, Interleukin / Q000032:analysis / Q000172:deficiency / Q000378:metabolism; D053722:Receptors, Interleukin-17; D011994:Recombinant Proteins / Q000032:analysis / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects; D013950:Thymus Gland / Q000166:cytology
D000911:Antibodies, Monoclonal; D016207:Cytokines; C491673:Il17ra protein, mouse; D007142:Immunoglobulin gamma-Chains; D015851:Interleukin-7; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin; D053722:Receptors, Interleukin-17; D011994:Recombinant Proteins