CD8⁺ suppressor‐mediated regulation of human CD4⁺ T cell responses to glutamic acid decarboxylase 65

Abstract

Although potentially autoreactive T cells are present even in healthy subjects, most individuals do not develop autoimmune disease. It has been well demonstrated that CD4 + CD25 + regulatory T cells play a significant role in controlling the expansion of autoreactive T cells in the periphery. However, some healthy individuals exhibit measurable responses to self peptide even in the presence of CD4 + CD25 + regulatory cells. This article describes the regulation of human CD4 + T cell responses to glutamic acid decarboxylase 65 (GAD65), an autoantigen implicated in type-1 diabetes, by autologous CD8 + suppressor T cells. In cells cultured from healthy individuals, the inclusion of autologous CD8 + T cells at physiological levels resulted in a dramatic decrease in the magnitude of in vitro CD4 + T cell responses to GAD65 peptide. Based on transwell experiments, the observed suppression was cell contact-dependent. However, antibody blocking studies indicated that suppression was mediated by IL-10. Cell fractionation studies suggested that CD8 + suppressor T cells originate from the CD45RA + CD27 -population. The suppression of CD4 + T cell responses to GAD65 in healthy individuals raises the possibility that CD8 + suppressor T cells play an important role in controlling potentially autoreactive T cells in the general population.

Functions of Anti-MAGE T-Cells Induced in Melanoma Patients under Different Vaccination Modalities

“…In doing so, it may however promote viral persistence (38) or inhibit antitumor immunity (39). It was shown to be produced by human CD8 + lymphocytes displaying suppressive activity (16)(17)(18)(19). Our IL-10-producing CTL clones had no detectable suppressive activity, as shown in Fig.…”

“…Because a few reports describe the secretion of IL-10 by human CD8 + lymphocytes displaying suppressive activity (16)(17)(18)(19), we tested whether our IL-10-producing anti-MAGE-3.A1 CTL clones inhibited the proliferation of cocultured allogenic bulk populations of CD4 + CD25…”

Prevention of spontaneous immune-mediated diabetes development in the LEW.1AR1-iddm rat by selective CD8+ T cell transfer is associated with a cytokine shift in the pancreas-draining lymph nodes

“…There is cumulative evidence that CD8 + T cells may participate as effectors and as regulators in autoimmune diseases [16,[24][25][26][27][28]. A clear inhibitory interaction between regulatory CD8 + and autoreactive CD4 + T cells was found in experimental autoimmune encephalomyelitis [25,29] and also in human autoimmune diabetes [30][31][32]. In a mouse model of experimental autoimmune encephalomyelitis, CD8 + /CD28 − T cells provided protection by inhibiting upregulation of co-stimulatory molecules on antigenpresenting cells, thereby inhibiting activation and clonal expansion of autoaggressive CD4 + cells [26].…”

The Suppression of Murine Lupus by a Tolerogenic Peptide Involves Foxp3-Expressing CD8 Cells That Are Required for the Optimal Induction and Function of Foxp3-Expressing CD4 Cells

“…Tregs consist of different subpopulations of cells, with CD4 ϩ CD25 ϩ cells constituting a well-studied lineage of immunoregulatory T cells. The competence of all types of Tregs to modulate immune responses and maintain self-tolerance requires not only a sufficient numerical mass and functional suppressive abilities but also the orchestration of the various types of cells (13). CD8 Tregs, in addition to CD4 Tregs, constitute a major cell population that has been demonstrated to play an important role in autoimmune diseases, including experimental autoimmune encephalomyelitis (14), myasthenia gravis (15), and SLE (16).…”