T-cell-derived helper factor allows in vivo induction of cytotoxic T cells in nu/nu mice

Abstract

T-cell immunocompetence and diversity are thought to be generated in the thymus^1,2. This view is based on the findings that (1) T-cell ontogeny is thymus dependent^3,4, (2) the major histocompatibility restrictions of T-cell interactions are phenotypically related to the H–2 type of the thymus^5–9, and (3) the phenotypic manifestation of H–2-linked immune responsiveness parallels the restriction elements selected in thymus^10–12. However, it is unclear whether pre-thymic cells programmed to develop into T cells do already express a receptor diversity, also whether pre-thymic cells have the potential to react against self-antigens, and whether the mechanism of self-tolerance is initiated in the thymus by either elimination or suppression of self-reactive clones. If it were possible to confer on pre-thymic cells antigen-specific effector functions, the impact of the thymus on the generation of T-cell diversity and function could be analysed in more detail. In mice, the nude mutation lacks a functioning thymus^13,14; nu/nu mice possess a thymic rudiment which is epithelial in the embryo¹⁵ and a fibrous, cystic remnant in adult^15,16; this remnant is not populated by lymphoid cells^15–17. At present, the absence of immunocompetent T cells in nu/nu mice is explained by a lack of thymic differentiation and maturation of pre-thymic cells (reviewed in ref. 13). Here we report that injection of allogeneic stimulator cells plus a Lyt 1 T-cell-derived helper factor^18,19, termed interleukin 2 (for the system of nomenclature, see ref. 20) allows lymphocytes of nu/nu mice to differentiate in vivo into alloreactive cytotoxic T lymphocytes (CTLs).