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 journalArticlepeer-review

4 Scopus citations

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

ASJC Scopus subject areas

  • Immunology

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