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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

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

Published Date

  • December 2001

Published In

Volume / Issue

  • 126 / 3

Start / End Page

  • 511 - 518

PubMed ID

  • 11737070

Pubmed Central ID

  • PMC1906228

International Standard Serial Number (ISSN)

  • 0009-9104

Digital Object Identifier (DOI)

  • 10.1046/j.1365-2249.2001.01625.x


  • eng

Conference Location

  • England