Limiting dilution analysis of the suppressive effect mediated by alloantigen-primed cells

Immunology. 1980 Oct;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. In the present report, these negative allogeneic effects have been analysed in detail. Suppression was qualitatively and quantitatively similar when 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. Taken together, these data indicate that 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.

MeSH terms

  • Animals
  • Antibody Formation*
  • B-Lymphocytes / immunology
  • Cells, Cultured
  • Isoantigens / immunology*
  • Leukocyte Count
  • Lymphocyte Culture Test, Mixed
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Nude
  • T-Lymphocytes / immunology
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • Isoantigens