Fingerprints of anergic T cells

Abstract

Peripheral T cell tolerance may result from activation-induced cell death [1], anergy [1], and/or immune response modulation by regulatory T cells [2]. In mice that express a transgenic receptor specific for peptide 111-119 of influenza hemagglutinin presented by E(d) class II MHC molecules as well as hemagglutinin under control of the immunoglobulin-kappa promoter, we have found that anergic T cells [3] can also have immunoregulatory function and secrete IL-10 [4]. In order to obtain information on molecular mechanisms involved in anergy and immunoregulation, we have compared expression levels of 1176 genes in anergic, naive, and recently activated CD4+ T cells of the same specificity by gene array analysis. The results provide a plausible explanation for the anergic phenotype in terms of proliferation, provide new information on the surface phenotype of in vivo-generated anergic CD4+ T cells, and yield clues with regard to new candidate genes that may be responsible for the restricted cytokine production of in vivo-anergized CD4+ T cells. The molecular fingerprints of such T cells should enable the tracking of this small population in the normal organism and the study of their role in immunoregulation.

Paradoxical role of programmed death‐1 ligand 2 in Th2 immune responses in vitro and in a mouse asthma model in vivo

“…This provides direct evidence for PD-1 as a negative regulator of immune responses in vivo [13]. PD-1 mRNA is expressed at high levels in CD4 + CD25 + regulatory T cells (Treg) and anergic T cells [14,15], suggesting the possible involvement of PD-1 in regulating Treg function and T cell tolerance.…”

Fasciola hepatica tegumental antigens induce anergic‐like T cells via dendritic cells in a mannose receptor‐dependent manner

“…Studies on anergenic T cells have uncovered a complex mechanism involving a number of negative regulators [33] including EGR2, EGR3 and the E3-ubiquitin ligases, GRAIL, ITCH, and CblB [34]. Both EGR2 and EGR3 are involved in the induction and maintenance of T-cell anergy [35].…”

“…In our studies, IFN-γ production is not observed when splenocytes from infected or injected mice are stimulated with FhTeg and in the case of infection even after the addition of IL-2. Similarly, FhTeg restimulated cells do not exhibit other characteristics associated with exhausted T cells such as high deletion of cells and apoptosis, which further supports its role in the induction of anergy.Studies on anergenic T cells have uncovered a complex mechanism involving a number of negative regulators [33] including EGR2, EGR3 and the E3-ubiquitin ligases, GRAIL, ITCH, and CblB [34]. Both EGR2 and EGR3 are involved in the induction and maintenance of T-cell anergy [35].…”

PD-L1-deficient mice show that PD-L1 on T cells, antigen-presenting cells, and host tissues negatively regulates T cells

“…Up-regulation of PD-L1 during Th1-driven inflammation might serve as a negative feedback mechanism for controlling responses in the target organ and limit pathogenic T cell responses in the brain. Furthermore, PD-1 mRNA is highly expressed in CD4 ϩ CD25 ϩ T regulatory cells (Treg) which have been shown to regulate EAE (24,25). Thus, the increased MOG-specific CD4 ϩ T cell responses in PD-L1 Ϫ/Ϫ mice might reflect multiple negative regulatory functions for PD-L1: (i) limiting expansion and͞or Th1 differentiation of naïve CD4 ϩ T cells, (ii) negatively regulating reactivation of MOG-specific effector CD4 ϩ T cells in the target organ, and (iii) limiting expansion of antigen-specific T cells through engagement of PD-1 on Tregs.…”