An interleukin-7 internet for intestinal intraepithelial T cell development: knockout of ligand or receptor reveal differences in the immunodeficient state.
Both interleukin-7 (IL-7) and IL-7 receptor (R) gene knockout (IL-7-/- and IL-7R-/-) mice were employed in order to directly investigate the importance of the IL-7 and IL-7R signaling pathway for the development of intestinal intraepithelial lymphocytes (IEL). Loss of the IL-7R-specific gene resulted in complete deficiency of the gamma delta T cell lineage with lack of V gamma 4- and V gamma 7-specific messages in the epithelium of the gastrointestinal (GI) tract in comparison to control mice of the same genetic background (approximately 40%). Disruption of the IL-7-specific gene resulted in marked, but not complete depletion of gamma delta T cells (2-3%) in IEL. Furthermore, mRNA for both V gamma 4 and V gamma 7 genes were detected in the gamma delta IEL subset of IL-7-/- mice. The subtle differences between IL-7-/- and IL-7R-/- mice suggest that although IL-7 controls most of the expansion and/or development of gamma delta IEL, another ligand binding to the IL-7R also plays a discernable role. Furthermore, alpha beta IEL developed more slowly in IL-7R-/- mice when compared with ligand knockouts; however, the frequency of IEL T cells subsequently increased with age and normal levels of CD3+ T cells expressing the alpha beta TCR were detected by 2 and 3 months of age in IL-7-/- and IL-7R-/- mice, respectively. The direct comparison of IL-7-/- and IL-7R-/- mice clearly supports the hypothesis that both IL-7 and another IL-7R binding molecule can influence the development of gamma delta T cells in the intestinal epithelium.
Fujihashi
K
K
Department of Oral Biology, University of Alabama at Birmingham, Medical Center 35294-2170, USA. kohtarof@uab.edu
McGhee
J R
JR
Yamamoto
M
M
Peschon
J J
JJ
Kiyono
H
H
D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D018928:Immunity, Mucosal; D015851:Interleukin-7 / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D018123:Receptors, Interleukin / Q000502:physiology*; D020395:Receptors, Interleukin-7; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D015703:Antigens, CD; D016207:Cytokines; D015851:Interleukin-7; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018123:Receptors, Interleukin; D020395:Receptors, Interleukin-7