Decreased level of T cell receptor expression by Down syndrome (trisomy 21) thymocytes.
Individuals with Down syndrome (DS) have an enhanced susceptibility to viral and bacterial infections. Previous studies by our laboratory demonstrated alterations in the proportions of peripheral T cell subpopulations and decreased proliferative, interleukin-2, and antibody responses to viral and bacterial antigens in DS. These data suggested that DS lymphocytes have a diminished ability to recognize and respond to specific antigen. It has been proposed that the abnormalities in T cell function in DS may be a result of aberrant T cell maturation within the DS thymus. Therefore, we examined by immunofluorescence and flow cytometry the cell surface expression of the alpha,beta chains of the T cell receptor (TCR alpha,beta) and the associated CD3 molecule on thymocytes from 10 DS and 27 control children. A significantly smaller proportion of cells expressing high levels of TCR alpha,beta was observed in DS thymuses compared to controls (17.0% vs. 34.3%, respectively; P less than 0.01). A similar observation was made for CD3, a molecule responsible for signal transduction through the TCR, where a lower proportion of cells expressing high levels of CD3 was found in DS compared to controls (18.4% vs. 43.3%, respectively; P less than 0.001). These data are evidence for aberrant T cell maturation in DS. In addition, our findings of decreased acquisition of high levels of the molecules which are critical for antigen-specific recognition by T cells suggest a possible mechanism for the decreased T cell function found in individuals with DS.
Murphy
M
M
Department of Pediatrics, University of California, San Francisco 94143.
Lempert
M J
MJ
Epstein
L B
LB
D015703:Antigens, CD / Q000032:analysis*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis*; D017252:CD3 Complex; D002648:Child; D004314:Down Syndrome / Q000276:immunology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D011948:Receptors, Antigen, T-Cell / Q000032:analysis*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D011948:Receptors, Antigen, T-Cell