At low precursor frequencies, the T‐cell response to chronic self‐antigen results in anergy without deletion

Abstract

The behavior of self-reactive T cells in the peripheral immune system has often been studied by following the fate of adoptively transferred antigen-specific T cells in antigen expressing mice. In most cases, after a period of expansion, such cells undergo a slow clonal deletion, accompanied by the onset of anergy and/or suppression in the remaining cells. Here, we demonstrate that at initial frequencies approaching those found in normal repertoires, it is possible to completely avoid deletion and still maintain peripheral tolerance. At starting numbers of <1000 T cells, stimulation by chronic self-antigens resulted in a period of robust clonal expansion, followed by a steady plateau phase extending beyond four months. Despite their stable persistence, the self-reactive T cells did not convert to a Foxp3+ fate. However, they displayed a considerable block in their ability to make IL-2, consistent with the onset of anergy – in a precursor frequency or deletion independent fashion.

Monophosphoryl Lipid A Enhances Efficacy of a Francisella tularensis LVS-Catanionic Nanoparticle Subunit Vaccine against F. tularensis Schu S4 Challenge by Augmenting both Humoral and Cellular Immunity

“…Nonadherent cells harvested after 72 h of coculture were also subjected to staining. Staining protocols were carried out essentially as previously described (39,66,67). Briefly, cells were incubated on ice in 2% FBS-PBS.…”

Immune Cells and Inflammation in Diabetic Nephropathy

“…The nature of CD4+ anergy is not well known, with much of the current information on this phenomenon having been gleaned from analogous study on CD8+ T cells. Anergetic T cells are understood to have very weak, if any, capability of sending further stimulation to other cells, especially via cytokine production [ 67 ]. Several types of viral infections are known to induce T cell anergy as a means of escaping immune suppression, and TGF β signaling is thought to be involved, but much remains to be clarified.…”

Functionally responsive self‐reactive B cells of low affinity express reduced levels of surface IgM

“…The notion that lymphocytes are capable of modifying their activation threshold following encounter with antigen was initially suggested by Grossman and Paul, and is referred to as the tunable activation threshold model [45,46]. Adoptive transfer studies utilizing Tg (5C.C7) CD4 + T cells support the tunable activation threshold model and suggest that signaling is modulated in response to self-Ag in part by upregulation of CD5 [47][48][49]. In this model, T cells avoid clonal deletion and attain tolerance to the steady state level of self-Ag without a concomitant reduction in surface TCR.…”