Spontaneous loss and alteration of antigen receptor expression in mature CD4+ T cells.

Abstract

The TCR/CD3 complex plays a central role in antigen recognition and activation of mature T cells, and, therefore, abnormalities in the expression of the complex should induce unresponsiveness of T cells to antigen stimulus. Using flow cytometry, we detected and enumerated variant cells with loss or alteration of the surface TCR/CD3 expression among human mature CD4+ T cells. The presence of variant CD4+ T cells was demonstrated by isolating and cloning them from peripheral blood, and their abnormalities can be accounted for by alterations in TCR expression such as defects of protein expression and partial protein deletion. The variant frequency in peripheral blood increased with aging in normal donors and was highly elevated in patients with ataxia telangiectasia, an autosomal recessive inherited disease with defective DNA repair and variable T cell immunodeficiency. These findings suggest that such alterations in TCR expression are induced by somatic mutagenesis of TCR genes and can be important factors related to age-dependent and genetic disease-associated T cell dysfunction.

T cells and aging (update February 1999)

“…There is a significant age-associated increase in the number of CD4+ T cells expressing variant (presumably mutant) TCR, as Kyoizumi et al demonstrated using 127 normal donors from < 10 to > 80 yr. old (637). Age-related increases in mutations of HLA genes have also been reported (638).…”

Recent advances in pathogenesis and management of hypereosinophilic syndromes

“…Interestingly, m-HES patients require lower doses of imatinib (often 100 mg/day, and sometimes even less) than patients with CML to induce and maintain remission. In vitro data have shown that the concentration of imatinib required to inhibit cells expressing the F/P fusion by 50% (IC 50 ) is over 100 times lower than that required to inhibit cells expressing the BCR-ABL fusion observed in CML (16). As a consequence, adverse effects of imatinib, most of which are dose-dependent, have been encountered less frequently in studies evaluating effects in m-HES patients.…”

A Positive Correlation between the Precursor Frequency of Cytotoxic Lymphocytes to Autologous Epstein‐Barr Virus‐Transformed B Cells and Antibody Titer Level against Epstein‐Barr Virus‐Associated Nuclear Antigen in Healthy Seropositive Individuals

“…The cytotoxic activity of 100 /11 samples of the cultures was examined against autologous and allogeneic EBV-LCLs using the 16 hr 51Cr-release assay described above. On the next day of the cytotoxicity assay, the cell-surface phenotypes of cells from wells that showed cytotoxic activity were analyzed using flow cytometry, as described previously (16). Cells were trichotomized and reacted with PE-labeled MAb followed by FLlabeled MAb according to the method described by the supplier.…”