Genesis of progressive T-cell deficiency owing to a single missense mutation in the common gamma chain gene

A. S. Goldman, K. H. Palkowetz, H. E. Rudloff, D. V. Dallas, F. C. Schmalstieg

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Patients with a moderate X-linked combined immunodeficiency (XCID) owing to a single missense mutation in the common gamma chain (γc) gene (L→Q271) were found to have a progressive T-cell deficiency. Blood T cells from four older subjects with XCIDL→Q271 were studied to ascertain the basis of that progression. Few CD4+ T cells displayed the phenotype (CD45RA+ CD62L+) or deletion circles from T-cell receptor (TCR) Vβ-gene rearrangements found in recent thymic emigrants. These deficiencies were more severe in older males with XCIDL→Q271. Relative frequencies of fresh CD4+ and CD8+ T cells that bound annexin V, an early indicator of programmed cell death, or propidium iodide, an indicator of cell necrosis, were greater in XCIDL→Q271 T cells than in normal fresh T cells. The binding of annexin V and propidium iodide to XCIDL→Q271 T cells increased marginally after stimulation with anti-CD3, but binding by fresh or stimulated XCIDL→Q271 T cells exceeded that found in normal stimulated T cells. Also, telomeres from XCIDL→Q271 CD4+ T cells were shortened in these patients compared to normal young adults. It therefore appears that the thymus is dysfunctional and that mature T cells are not effectively rescued from apoptosis or replication senescence via γc-mediated pathways in XCIDL→Q271.

Original languageEnglish (US)
Pages (from-to)582-591
Number of pages10
JournalScandinavian Journal of Immunology
Volume54
Issue number6
DOIs
StatePublished - 2001
Externally publishedYes

Fingerprint

Missense Mutation
T-Lymphocytes
Genes
Propidium
Annexin A5
X-Linked Combined Immunodeficiency Diseases
T-Cell Receptor Genes
Gene Rearrangement
Telomere
Thymus Gland
Young Adult
Blood Cells
Cell Death
Necrosis
Apoptosis
Phenotype

ASJC Scopus subject areas

  • Immunology

Cite this

Genesis of progressive T-cell deficiency owing to a single missense mutation in the common gamma chain gene. / Goldman, A. S.; Palkowetz, K. H.; Rudloff, H. E.; Dallas, D. V.; Schmalstieg, F. C.

In: Scandinavian Journal of Immunology, Vol. 54, No. 6, 2001, p. 582-591.

Research output: Contribution to journalArticle

Goldman, A. S. ; Palkowetz, K. H. ; Rudloff, H. E. ; Dallas, D. V. ; Schmalstieg, F. C. / Genesis of progressive T-cell deficiency owing to a single missense mutation in the common gamma chain gene. In: Scandinavian Journal of Immunology. 2001 ; Vol. 54, No. 6. pp. 582-591.
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