Defective dendritic cell maturation in a child with nucleotide excision repair deficiency and CD4 lymphopenia

Clin Exp Immunol. 2001 Dec;126(3):511-8. doi: 10.1046/j.1365-2249.2001.01625.x.


We report a case of a combined immunodeficiency (CID) in a child affected by trichothiodystrophy (TTD) characterized by an altered response to ultraviolet (UV) light due to a defect in the XPD gene. The XPD gene encodes a subunit of the transcription factor II H (TFIIH), a complex involved in nucleotide-excision repair (NER) and basal transcription. Our patient showed neurological and immune system abnormalities, including CD4 + lymphopenia never previously reported in TTD patients. In vitro immunological studies revealed a marked reduction in T-cell proliferation in response to mitogens and CD3 cross-linking which was partially recovered by the addition of anti-CD28 antibody or exogenous interleukin-2. The patient's T cells displayed alterations in T-cell receptor (TCR/CD3) proximal signalling characterized by marked reduction in Lck kinase activity coupled with a constitutive hyperactivation of Fyn kinase. Despite these alterations, normal levels of Lck and Fyn proteins were detected. The role of antigen-presenting cells (APCs) in the pathogenesis of the T-cell defect was investigated by analysing dendritic cells (DCs) generated from the patient's blood monocytes. In these cells, flow cytometry revealed significantly reduced expression of the CD86 co-stimulatory molecules and HLA glycoproteins. In addition, the patient's DCs showed a decreased ability to stimulate naive T lymphocytes. Overall, the results of our study suggest that a defective TFIIH complex might result in alterations in T cells and DC functions leading to a severe immunodeficiency.

Publication types

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

MeSH terms

  • CD4-Positive T-Lymphocytes
  • Cell Differentiation
  • Child, Preschool
  • DNA Helicases*
  • DNA Repair* / genetics
  • DNA-Binding Proteins*
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Dendritic Cells / pathology*
  • Genes, Recessive
  • Hair / abnormalities
  • Humans
  • Ichthyosis / genetics
  • Intellectual Disability / genetics
  • Lymphopenia / genetics
  • Lymphopenia / immunology*
  • Lymphopenia / pathology*
  • Male
  • Photosensitivity Disorders / genetics
  • Proteins / genetics
  • Severe Combined Immunodeficiency / genetics
  • Severe Combined Immunodeficiency / immunology
  • Severe Combined Immunodeficiency / pathology
  • Signal Transduction
  • Syndrome
  • Transcription Factor TFIIH
  • Transcription Factors / genetics
  • Transcription Factors, TFII*
  • Xeroderma Pigmentosum Group D Protein


  • DNA-Binding Proteins
  • Proteins
  • Transcription Factors
  • Transcription Factors, TFII
  • Transcription Factor TFIIH
  • DNA Helicases
  • Xeroderma Pigmentosum Group D Protein
  • ERCC2 protein, human