LIMITING DILUTION ANALYSIS OF THE SUPPRESSIVE EFFECT MEDIATED BY ALLOANTIGEN-PRIMED CELLS

  • 1 January 1980
    • journal article
    • research article
    • Vol. 41  (2) , 399-406
Abstract
T cells primed in mixed lymphocyte culture exert both positive and negative allogeneic effects on B cells expressing the appropriate alloantigens. The positive and negative effects can be separated by limiting dilution analysis: positive effects, measured by production of anti-sheep erythrocyte antibody, are revealed when low numbers of primed T cells are added to cultures of B cells and sheep erythrocytes, while suppression of the response occurs at higher T cell inputs. These negative allogeneic effects were analyzed in detail. Suppression was qualitatively and quantitatively similar when [mouse] helper T cell activity was provided from any of several sources. Helper T cells in the alloantigen-primed population gave rise to active T cell replacing factors even under conditions in which all microcultures were suppressed and suppressor cells were present at a high multiplicity in every well. The degree of suppression was influenced by the multiplicity of B cells in culture; as the number of B cells increased, more suppressor cells were required to inactivate a microculture. Apparently the targets of the suppressor cells are B cells and not helper T cells or T cell replacing factors. Although suppressor cells can prevent the activation of B cells by the more frequent helper cells in the primed T-cell population, detailed analysis of the stoichiometry of the suppression demonstrated that a single suppressor cell is capable of inactivating only a limited number of B cells, suggesting that a ratio-dominance model of suppression is operative in this system.