Development of T Cells within the Thymus

Abstract

There are many unanswered questions concerning the role of the thymus in the generation of T lymphocytes. Questions about the influence of the thymus on the generation of the T cell receptor repertoire are particularly pertinent following recent rapid progress in knowledge of the genetic control and structure of the receptor¹. Although it is not clear whether the recombination of germ line V-, D- and J- gene segments which forms the basis for coding diverse variable regions of T cell receptors occurs during lymphocyte maturation within the thymus² or at an earlier pre-thymic stem cell stage,³ there is considerable evidence that the thymus shapes the T cell receptor repertoire. Thus T cells show major histocompatibility (MHC) antigen restriction in their response to foreign antigens and tolerance to “self” MHC antigens which maps to the MHC haplotype of the thymus within which they develop⁴. In particular, MHC antigens expressed on thymic stromal cells may select for survival lymphocytes which express the appropriate receptors. This notion is supported by the high rate of cell death within the thymus, presumably of non-compatible cells, although non-productive rearrangements of T cell receptor genes might occur at high frequency resulting in cell death⁵.