T-cell repopulation following neonatal injection of non-obese diabetic (NOD) mice with anti-T-cell antibodies.
Non-obese diabetic (NOD) mice injected with CD3 antibody as newborns have a reduced incidence of diabetes, raising the possibility that the neonatal injection caused a long-lasting change in circulating T cells. The present study shows that NOD and BALB/c mice injected with soluble CD3 antibody in the first 2 days of life sustained an 80-95% reduction in the number of circulating T cells lasting for 2-3 weeks, with T cells returning after 4 weeks, and reaching control values after 6 weeks. The T cells which appeared in intact mice 4-6 weeks after injection showed no excess of T-cell receptor (TcR) delta expressing cells. They had a similar distribution into CD4 and CD8 subsets as uninjected controls, and a similar usage and cell surface expression of four T-cell receptor V beta families. Labelled CD3 antibody was detected in the serum for up to 2 weeks after injection into neonates and was enriched in the thymus. Adoptively transferred T cells continued to be cleared from the circulation for 4 weeks following antibody injection. The properties of T cells which had been exposed to CD3 neonatally were investigated in animals who were first injected with CD3 antibody and then thymectomized. These animals had reduced numbers of T cells at 12 weeks of age. The surviving T cells showed a Ca2+ flux when stimulated but their proliferation in response to concanavalin A (Con A) was reduced, even in the presence of irradiated accessory cells or T-cell supernatant co-stimulator factors. Although the representation of four different V beta families was the same as in the uninjected controls, the density of expression of the T-cell receptor was reduced. The data indicate that the limited number of T cells which survive the injection are functionally deficient and that an intact thymus is required for full T-cell repopulation following neonatal CD3 injection into NOD mice.
Hayward
A
A
Department of Pediatrics, University of Colorado School of Medicine, Denver 80262.
Shriber
M
M
Kubo
R
R
McDuffie
M
M
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology* / Q000378:metabolism; D017252:CD3 Complex; D002455:Cell Division / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D011948:Receptors, Antigen, T-Cell / Q000276:immunology* / Q000378:metabolism; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D011948:Receptors, Antigen, T-Cell