Some quantitative aspects of T-cell repertoire selection: the requirement for regulatory T cells

Summary: How the adaptive immune system achieves self–non-self discrimination is not well understood, and in this article consideration is given to some of the quantitative aspects of this problem. In particular, the modification of the T-cell repertoire as a result of clonotypic deletion in the thymic cortex is discussed and shown to make a major contribution to the achievement of self-tolerance. An evaluation is also made of the benefit of MHC restriction in preventing clonal deletion in MHC heterozygotes from being more profound than it is in homozygotes, despite the approximately twofold increase in the presentation of self-peptides in the thymus in heterozygotes. The effect that receptor editing may have on the efficiency of positive selection is estimated. Finally, the conclusions from these considerations are used to suggest why a subset of T cells, the regulatory T cells, are required to control immune responses to certain self-antigens. The potential value of regulatory T cells to the control of inflammation induced by pathogens is also briefly discussed.