Inborn errors of immunity underlying defective T-cell memory

Curr Opin Allergy Clin Immunol. 2023 Dec 1;23(6):491-499. doi: 10.1097/ACI.0000000000000946. Epub 2023 Oct 5.

Abstract

Purpose of review: T-cell memory is a complex process not well understood involving specific steps, pathways and different T-cell subpopulations. Inborn errors of immunity (IEIs) represent unique models to decipher some of these requirements in humans. More than 500 different IEIs have been reported to date, and recently a subgroup of monogenic disorders characterized by memory T-cell defects has emerged, providing novel insights into the pathways of T-cell memory generation and maintenance, although this new knowledge is mostly restricted to peripheral blood T-cell memory populations.

Recent findings: This review draws up an inventory of the main and recent IEIs associated with T-cell memory defects and their mice models, with a particular focus on the nuclear factor kappa B (NF-κB) signalling pathway, including the scaffold protein capping protein regulator and myosin 1 linker 2 (CARMIL2) and the T-cell co-stimulatory molecules CD28 and OX-40. Besides NF-κB, IKZF1 (IKAROS), a key transcription factor of haematopoiesis and STAT3-dependent interleukin-6 signals involving the transcription factor ZNF341 also appear to be important for the generation of T cell memory. Somatic reversion mosaicism in memory T cells is documented for several gene defects supporting the critical role of these factors in the development of memory T cells with a potential clinical benefit.

Summary: Systematic examination of T-cell memory subsets could be helpful in the diagnosis of IEIs.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gene Expression Regulation
  • Humans
  • Memory T Cells*
  • Mice
  • NF-kappa B* / metabolism
  • Signal Transduction
  • T-Lymphocyte Subsets

Substances

  • NF-kappa B