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

L. Racioppi, C. Cancrini, M. L. Romiti, F. Angelini, S. Di Cesare, E. Bertini, S. Livadiotti, M. G. Gambarara, G. Matarese, F. Lago Paz, M. Stefanini, P. Rossi

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)511-518
Number of pages8
JournalClinical and Experimental Immunology
Issue number3
Publication statusPublished - 2001


  • Anergy
  • Combined immunodeficiency (CID)
  • Dendritic cells (DCs)
  • T lymphocytes
  • Trichothiodystrophy (TTD)

ASJC Scopus subject areas

  • Immunology


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