T cells with gamma/delta T cell receptors (TCR) of intestinal type are preferentially expanded in TCR-alpha-deficient lpr mice.
Fas-mediated apoptosis is essential for activation-induced cell death of alpha/beta T cells, but it is not clear what role, if any, it plays in regulating other components of the immune system. To study the role of Fas in gamma/delta T cell development, Fas-deficient lpr mice were bred with T cell receptor alpha gene-ablated (TCR-alpha-/-) mice to generate mice deficient in one or both genes. The TCR-alpha-/-, lpr/lpr mice had a nearly 10-fold increase in total lymph node cell (LNC) number compared with Fas-intact TCR-alpha-/- mice, because of expansion of TCR-gamma/delta+ and TCR-beta+ cells. In Fas-intact TCR-alpha-/- mice, approximately one third of the LNCs expressed TCR-gamma/delta. These were evenly divided between the CD4-, CD8-alpha+ and the CD4-, CD8- subsets, and rarely expressed the B220 epitope of CD45. In contrast, in TCR-alpha-/-, lpr/lpr mice, TCR-gamma/delta+ cells comprised half of the LNCs and were primarily CD4-, CD8-, and B220+. Moreover, Fas deficiency in TCR-alpha-/- mice caused a preferential expansion of gamma/delta T cells expressing variable region genes characteristic of intestinal intraepithelial lymphocytes. These results demonstrate a role for Fas in regulating the gamma/delta T cell contribution to peripheral lymph nodes. This mechanism may be most important in limiting the access of activated intestinal intraepithelial lymphocytes to the peripheral lymphoid system.
Hughes
D P
DP
Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520-8011, USA.
Hayday
A
A
Craft
J E
JE
Owen
M J
MJ
Crispe
I N
IN
D000818:Animals; D000954:Antigens, Surface / Q000235:genetics / Q000502:physiology*; D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D002455:Cell Division; D002465:Cell Movement; D004251:DNA Transposable Elements / Q000235:genetics; D016130:Immunophenotyping; D007413:Intestinal Mucosa / Q000276:immunology* / Q000473:pathology; D008198:Lymph Nodes / Q000473:pathology*; D018655:Lymphocyte Count; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000172:deficiency* / Q000235:genetics; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis* / Q000235:genetics; D013047:Specific Pathogen-Free Organisms; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D019014:fas Receptor
D000954:Antigens, Surface; D004251:DNA Transposable Elements; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D019014:fas Receptor