Nat Immunol 2002 Jul 1
Apostolou I, Sarukhan A, Klein L, Von Boehmer H.
Harvard Medical School, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA.
T cell receptor agonists can induce the differentiation of regulatory T (T(R)) cells.
We report here that the immunoglobulin kappa controlled expression of an agonist in different cell types correlated with the phenotype of the generated T(R) cells.
We found that aberrant expression on thymic stroma yielded predominantly CD4(+)CD25(+) T(R) cells, which under physiological conditions may be induced by ectopically expressed organ-specific antigens and thus prevent organ-specific autoimmunity.
Expression of the agonist antigen by nonactivated hematopoietic cells produced mostly CD4(+)CD25(-) T(R) cells.
This subset can be derived from mature monospecific T cells without "tutoring" by other T cells and can be generated in the absence of a functioning thymus.
Suppression of CD4(+) T cell proliferative responses by both CD25(+) and CD25(-) subsets was interleukin 10 (IL-10) independent and was overcome by IL-2.
These data suggest that distinct pathways can be exploited to interfere with unwanted immune responses.