Development of the T cell receptor repertoire in lpr mice.
The development of double-negative (DN; CD4-, CD8-) T cells and their relationship with other T cell subsets in lpr mice remain poorly understood. Based on studies identifying lpr as a mutation in the fas gene, it has been hypothesized that defective apoptosis in the thymus abnormally affects T cell development and results in the lpr phenotype. A review of studies of T cell receptor repertoires in lpr mice, however, suggests that thymic events are mostly normal in lpr mice. Thus, a global defect in negative selection is not apparent in any T cell population, and positive selection of CD4+ and CD8+ subsets appears to be normal. Surprisingly, repertoire studies also suggest that the majority of DN T cells are positively selected on class I, but not class II, MHC molecules. Furthermore, the expansion of the DN T cell population appears to be driven by abnormal peripheral events. Together, these results provide new insights into the role of fas in T cell development and the aberrant T cell lymphoproliferation in lpr mice.
Rozzo
S J
SJ
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
Eisenberg
R A
RA
Cohen
P L
PL
Kotzin
B L
BL
D000818:Animals; D015395:Histocompatibility Antigens Class I / Q000502:physiology; D000949:Histocompatibility Antigens Class II / Q000502:physiology; D007108:Immune Tolerance / Q000235:genetics; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000502:physiology*
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D016693:Receptors, Antigen, T-Cell, alpha-beta