Expression of a T cell receptor γ-chain (Vγ1.1Jγ4Cγ4) transgene in mice influences T cell receptor ontogeny and thymic architecture during development

Abstract

In this report, we have characterized T cell ontogeny in mice transgenic for the Vγ1.1Jγ4Cγ4 (TcRγ4) TCR chain gene by analyzing the T cell surface phenotype and microarchitecture of the transgenic lymphoid organs during development. The first wave of Vγ3Jγ1Cγ1 TCR+ thymocytes that appear in the thymus at day 14 of gestation were virtually absent in the TCRγ4 transgenic mice. However, comparable levels of total γδ+ thymocytes were present in the TCRγ4 transgenic mice, suggesting that these thymocytes expressed a transgene receptor. In addition, the appearance of significant numbers of TCR αβ+ T cells occurred earlier (day 17 of fetal development) in the transgenic thymus. After birth, thymuses from TCRγ4 transgenic mice were characterized by a consistent increase in the number of TCR γδ+ thymocytes and a transient increase (between 2 and 4 wk of age) in the absolute number of TCR+ thymocytes (2- to 4-fold) compared with thymuses from normal mice. Immunohistologic analysis of the thymus, spleen, and lymph nodes from 2-day and 3-wk-old transgenic mice showed significant differences to controls only in regions harboring mature, functional T cell subsets which may be the result of bidirectional signaling between lymphocyte subsets (influenced by transgene expression) and stromal elements. The results demonstrate that striking differences, leading to the earlier appearance of mature T cells, occurred in both the fetal and neonatal thymus and periphery of mice that expressed a TCRγ4 transgene. These findings are consistent with the hypothesis that expression of the TCRγ4 chain gene, early in ontogeny, has a positive influence on the development of the T cell compartment.