Three day neonatal thymectomy selectively depletes NK1.1+ T cells.
Neonatal thymectomy of mice 3 days after birth but not at birth leads to T cell-mediated, organ-specific, autoimmune disease in a strain-dependent manner. The mechanisms that lead to disease in this model remain unknown, but the answer may lie in a deficiency of thymus-dependent cells or factors. One candidate is the relatively rare population of NK1.1 + T cells (NKT cells). Conventional alphabetaTCR+ T cells appear in the thymus from days 17-18 of embryogenesis and start emigrating to the periphery around birth, whereas the development of NKT cells is thought to be delayed until at least 1 week after birth. We have confirmed this to be the case in both (BALB/c x C57BL/6)F1 (autoimmune susceptible) and C57BL/6 (autoimmune resistant) mice. Moreover, examination of T cells (in spleen, lymph nodes, liver and bone marrow) from mice following 3 day neonatal thymectomy revealed a significant reduction in the presence of NKT cells in all tissues. However, the extent of depletion was generally more pronounced in (BALB/c x C57BL/6)F1 than in C57BL/6 mice, and the few remaining NKT cells in C57BL/6 mice were enriched for a CD4-CD8int subset which is absent from the thymus and may represent a distinct lineage of thymus-independent NKT cells. Given mounting evidence of a role for NKT cells in protection from autoimmune disease, it is possible that their specific removal by neonatal thymectomy may contribute to the susceptibility of these mice to autoimmune disease.
Hammond
K
K
Department of Pathology and Immunology, Monash University Medical School, Prahran, Victoria, Australia.
Cain
W
W
van Driel
I
I
Godfrey
D
D
D000818:Animals; D000831:Animals, Newborn; D017252:CD3 Complex / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis; D002454:Cell Differentiation / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D013934:Thymectomy; D013950:Thymus Gland / Q000502:physiology
D017252:CD3 Complex; D015704:CD4 Antigens