In vivo ligation of CD3 on neonatal scid thymocytes blocks gamma-irradiation-induced TCRbeta rearrangements and thymic lymphomagenesis.
Several studies have shown that the developmental arrest of severe combined immune deficiency (scid) thymocytes during the CD4(-)CD8(-) double negative (DN) to CD4(+)CD8(+) double positive (DP) transition can be overcome by a sub-lethal dose of ionizing radiation (IR). Concurrent with this developmental progression, IR also induces variable (diversity) joining (V(D)J) recombination at T cell receptor (TCR), delta, beta, and gamma, but not alpha loci. In addition, all irradiated scid mice succumb to thymic lymphoma. In this study, we demonstrate that scid neonates treated with anti-CD3 epsilon antibody become more resistant to the development of thymoma upon exposure to IR. It is known that the anti-CD3 epsilon antibody treatment induces T cell progression to the DP stage bypassing TCRbeta rearrangement. We show here that the resistance to tumor development is correlated with a reduction of TCRbeta rearrangements that are induced by IR. However, TCRgamma rearrangements were not altered by the antibody treatment. The particular effect of anti-CD3 epsilon antibody on TCRbeta rearrangements is likely attributed to a decline of the double negative thymocyte subset (DN3), in which TCRbeta rearrangements predominantly occur. These results suggest that the developmental stage of scid thymocytes can influence the effect of IR on TCR rearrangements as well as lymphomagenesis.
Martina
Cherie
C
Department of Microbiology, Molecular and Cellular Biology Program, Arizona State University, Tempe, AZ, 85287-2701, USA.
Wayne
Jay
J
Bell
Anthony
A
Chang
Yung
Y
D000818:Animals; D000906:Antibodies / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000528:radiation effects; D005720:Gamma Rays; D015321:Gene Rearrangement; D019674:Genes, T-Cell Receptor beta / Q000528:radiation effects; D008223:Lymphoma / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism*
D000906:Antibodies; D017252:CD3 Complex