Self-recognition specificity expressed by T cells from nude mice. Absence of detectable Ia-restricted T cells in nude mice that do exhibit self-K/D-restricted T cell responses.

Abstract

The T cell receptor repertoire for self major histocompatibility complex (MHC) ~ antigens and the Ir gene phenotype of responding T cells are not genetically determined but are acquired during ontogeny and are dictated by the MHC gene products of the host in which the T cells mature (1-3). The host element that determines the T cell self-recognition repertoire is the subject of much controversy, particularly when one considers separately the two major subsets of T cells, the H-2 K/D region-specific cytotoxic T lymphocytes (CTL) and the I region-restricted proliferating and helper T cells. On the one hand, studies with radiation-induced bone marrow (BM) chimeras or thymus-engrafted nude mice have indicated that peripheral T cells, both K/D and I region specific, recognize conventional antigens (Ag) in association with thymic MHC gene products (4-11), supporting a role for the thymus in the development of the MHC restriction specificity of T cells. However, several other investigations have failed to confirm such a unique role for the thymus. First, in radiation-induced BM chimeras, peripheral CTL with self-specificity for both thymic and extrathymic H-2 K/D Ag were observed (12-15). In vitro generation of CTL restricted to extrathymic K/D determinants was dependent on the addition of an exogenous source of T cell help (interleukin 2 [IL-2]) (13) or antigen-presenting cells (APC) carrying thymic H-2 I region determinants (12). Second, in congenitally athymic nude mice engrafted with an allogeneic thymus, splenic CTL with self-recognition specificity for both thymic and extrathymic (i.e., nude host) H-2 K/D Ag were observed (16). Again, in vitro generation of peripheral CTL specific for extrathymic K/D Ag was dependent on the addition of IL-2, while the generation of CTL restricted to thymic K/D determinants was not (16). The CTL system used in these studies, a trinitrophenyl (TNP)-modified self response, was shown

Absence of the Lyt-2-,L3T4+ lineage of T cells in mice treated neonatally with anti-I-A correlates with absence of intrathymic I-A-bearing antigen-presenting cell function.

“…Although the MHC phenotype of the nonlymphoid cells in the thymus has been implicated in the process that selects the MHC restriction specificities of T cells during development (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15), the precise intrathymic events determining acquisition of MHC restriction specificities remain unresolved. Some of the most basic questions regarding the development of class I-and class II-specific T cells are: With which MHC-bearing nonlymphoid cells do developing T cells interact?…”

Expression of Chicken DEC205 Reflects the Unique Structure and Function of the Avian Immune System

“…Education of T cells by self-recognition is presumed to take place as in mammals [16] and defects in this process produce autoimmunity [17].…”

Inhibition of Human CD4+CD25+high Regulatory T Cell Function

“…During ontogeny of the immune system, T cells expressing high-affinity TCRs for self Ags undergo clonal deletion in the thymus against a background of positive selection to MHC and self Ag (12,13). Thus, the resultant T cell repertoire can be viewed as, in essence, an autoreactive population with low-affinity receptors for self Ags.…”