Suppressor Cells and Immunoregulation

Abstract

We have described a model system of immunoregulation in which gene products associated with both the major histocompatibility complex and the heavy-chain immunoglobulin gene complex guide a series of cellular interactions. The Igh genetic restrictions may represent the use of internal images of antigen and idiotype as suppressor-T cell receptors. The data indicate that the T-cell and B-cell Igh products are distinct. The T cell-derived idiotype-like determinants are used for suppressor-T cell communications. The MHC restrictions generally involve the I-J subregion. These restrictions are imposed by the presentation of antigen or suppressor factor by specialized populations of I-J bearing accessory cells. The role of MHC products in the induction of suppressor cells has several homologies with the mechanisms responsible for the induction of H-2-restricted helper cells. First, I-region products on specialized presenting cells determine the specificity and genetic restrictions of the T cells. Thus, recognition of antigen in the context of I-A and I-E products is required for helper-T cell induction, and similarly the various suppressor-T cell subsets recognize antigen or suppressor factor presented in the context of I-J subregion-encoded antigens. Furthermore, the data suggest that the suppressor cells bear receptors for self I-J products. As an additional analogy between suppressor and helper cells, we have shown that in H-2-heterozygous F1 animals at least two populations of suppressor cells can be induced, one specific for each parental H-2 haplotype. The NP and ABA suppressor-cell pathways consist of multiple cellular elements, including at least three and possibly four distinct T-cell populations and two or more distinctive accessory cell populations. These are summarized in Figure 1. The specific soluble suppressor factors produced by each suppressor-T cell subset are involved in cellular communication processes. The terminal phases of the suppressor-cell cascade are antigen dependent but involve nonspecific bystander effects. In this review we have indicated the numerous homologies between the data in the hapten systems studied in our laboratories and the various other suppressor-cell models previously described in the literature.

Human regulatory T cells and autoimmunity

“…During the early 1980s, immunologists determined that two cellular mechanisms of tolerance induction could mediate peripheral regulation and the phenomena of induced CD4 + T cell nonresponsiveness. These two mechanisms were MHC-restricted T cell presentation of antigen to other T cells [1] and suppression via thymically derived 'suppressor' T cells [2]. Shortly after the discovery of MHC class II + CD4 + T cells in human peripheral blood (these cells are present in most mammalian species excluding mice [3]) [4,5], Kunkel and his colleagues [6] observed that autoimmune patients have a higher percentage of these cells in peripheral blood than healthy patients.…”

Therapeutic vaccination using CD4+CD25+antigen-specific regulatory T cells

“…1). Early on, CD8 ϩ T cells were identified that suppress immune responses through their direct cytotoxicity on antigen-bearing cells or through cryptic suppressor factors that were poorly characterized (2). However, during this early period, there were already hints that the quintessential helper T cells subset, CD4 ϩ T cells, also may have regulatory activity.…”

The Role of T regulatory Cells (Tregs) in the Development and Prevention of Type 1 Diabetes

“…This was followed by a flurry of activity, identifying several phenotypic markers for the various cell types involved in the suppression of excessive immune responsiveness (CD8 + suppressor effector cells, CD4 + suppressor-inducer cells etc. ), as well as several secreted suppressor factors [10,11]. The whole concept eventually fell into disrepute, mostly because of the lack of reproducible assays for these cells and lack of molecular identification of the factors involved [11,12].…”