Neonatal thymectomy (NTx), especially around day 3 after birth, causes various organ-specific autoimmune diseases in mice. This report shows that: (a) T cells expressing the interleukin 2 receptor alpha chains (CD25) ontogenically begin to appear in the normal periphery immediately after day 3, rapidly increasing within 2 wk to nearly adult levels (approximately 10% of CD3+ cells, especially of CD4+ cells); (b) NTx on day 3 eliminates CD25+ T cells from the periphery for several days; inoculation immediately after NTx of CD25+ splenic T cells from syngeneic non-Tx adult mice prevents autoimmune development, whereas inoculation of CD25- T cells even at a larger dose does not; and furthermore, (c) similar autoimmune diseases can be produced in adult athymic nu/nu mice by inoculating either spleen cell suspensions from 3-d-old euthymic nu/+ mice or CD25+ cell-depleted spleen cell suspensions from older, even 1-yr-old, nu/+ mice. The CD25- populations from neonates or adults are also similar in the profile of cytokine formation. These results, taken together, indicate that one aspect of peripheral self-tolerance is maintained by CD25+ T cells that sustain potentially pathogenic self-reactive T cells in a CD25- dormant state; the thymic production of the former is developmentally programmed to begin on day 3 after birth in mice. Thus, NTx on day 3 can, at least transiently, eliminate/reduce the autoimmune-preventive CD25+ T cells, thereby leading to activation of the self-reactive T cells that have been produced before NTx.
Skip Nav Destination
Article navigation
Article|
August 01 1996
Autoimmune disease as a consequence of developmental abnormality of a T cell subpopulation.
M Asano,
M Asano
Department of Immunopathology, Tokyo Metropolitan Institute of Geromology, Japan.
Search for other works by this author on:
M Toda,
M Toda
Department of Immunopathology, Tokyo Metropolitan Institute of Geromology, Japan.
Search for other works by this author on:
N Sakaguchi,
N Sakaguchi
Department of Immunopathology, Tokyo Metropolitan Institute of Geromology, Japan.
Search for other works by this author on:
S Sakaguchi
S Sakaguchi
Department of Immunopathology, Tokyo Metropolitan Institute of Geromology, Japan.
Search for other works by this author on:
M Asano
Department of Immunopathology, Tokyo Metropolitan Institute of Geromology, Japan.
M Toda
Department of Immunopathology, Tokyo Metropolitan Institute of Geromology, Japan.
N Sakaguchi
Department of Immunopathology, Tokyo Metropolitan Institute of Geromology, Japan.
S Sakaguchi
Department of Immunopathology, Tokyo Metropolitan Institute of Geromology, Japan.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1996) 184 (2): 387–396.
Citation
M Asano, M Toda, N Sakaguchi, S Sakaguchi; Autoimmune disease as a consequence of developmental abnormality of a T cell subpopulation.. J Exp Med 1 August 1996; 184 (2): 387–396. doi: https://doi.org/10.1084/jem.184.2.387
Download citation file:
Email alerts
Advertisement