Neonatal tolerance to Mls-1a determinants: Deletion or anergy of Vβ6 + T lymphocytes depending upon MHC compatibility of neonatally injected cells

Abstract

Recent investigations in mice revealed that natural immunologlcal tolerance to endogenous minor lymphocyte-stimulating locus 1a (MIs-1a antigen correlates primarily with deletion of Mls-1aspeciflc Vβ6+ T lymphocytes In the thymus. Similar mechanisms account for acquired tolerance in some Instancessince the neonatal injection of Mls-1 a-expressing MHC compatible cells in neonatal mice within the first 24 hof life causes clonal deletion of Vβ6+ T cells. Here we demonstrate that Vβ6+ T cells are not deleted In mice neonatally treated with Mls-1a spleen cells expressing allogenelc H-2 molecules. However, when such non-deleted Vβ6+ T cells were tested In vitro, no interleukin 2 (IL-2) secretion or proliferation was observed after Mls-1a stimulation. This non-responsive state could be overcome by addition of exogenous IL-2, consistent with the fact that Vβ6+ cells enlarged and expressed IL-2 receptors upon Mls-1a stimulation. Furthermore, the same neonatally treated mice showed In vitro functional unresponsiveness of cytotoxic T cells but not of IL-2-secreting cells specific for the tolerated allogeneic MHC antigens. Taken together, our data Indicate that neonatal tolerance to Mls-1a can be accomplished by either clonal deletion or clonal anergy, and that it does not necessarily correlate with tolerance to MHC determinants. © 1991 Oxford University Press.