Aberrant T-cell antigen receptor-mediated responses in Autoimmune Lymphoproliferative Syndrome

Academic Article


  • Autoimmune Lymphoproliferative Syndrome (ALPS) is a disorder of defective lymphocyte apoptosis due to mutations of the Fas receptor and other molecules in the Fas signaling pathway. In addition to accumulation of CD4- CD8- double-negative (DN) T cells, many patients display a dysregulated cytokine pattern with dysfunctional T cells, suggesting Fas defects may impact pathways of T-cell activation/differentiation. Here, we report two novel mutations in the Fas receptor resulting in an ALPS phenotype. Utilizing flow cytometry, we found anti-CD3 activated CD4+ T cells from these patients were incapable of fully upregulating activation markers (CD25, CD69, and CD40L) or producing interferon-γ and IL-2. Additionally, DN T cells were unable to transduce proximal T-cell antigen receptor signals or produce cytokines. Furthermore, DN T cells overexpressed CD57 and phenotypically resembled end-stage effector cells. As DN T cells were essentially anergic, the clinical manifestations of autoimmunity are more likely to be a consequence of aberrant cytokine secretion within the CD4+ T-cell subpopulation. © 2002 Elsevier Science (USA).
  • Published In

    Digital Object Identifier (doi)

    Author List

  • Goldman FD; Vibhakar R; Puck JM; Straus SE; Ballas ZK; Hollenback C; Loew T; Thompson A; Song K; Cook RT
  • Start Page

  • 31
  • End Page

  • 39
  • Volume

  • 104
  • Issue

  • 1