Once mutated, a single cell must expand into a clone before becoming significant for carcinogenesis. The forces driving clonal expansion and the obstacles that must be overcome are poorly understood. In a genetic mechanism, acquiring a second mutation conferring a proliferative advantage would enable the cell to expand autonomously. If carcinogen exposure instead induced a physiological change,...

Three patients with Barrett's esophagus who had cytogenetic abnormalities detected in their metaplastic epithelium developed high-grade dysplasia or adenocarcinoma during prospective surveillance over a period of 1.5 to 6 years. In the 3 cases, cytogenetic abnormalities that were associated with the most advanced histological lesions were present in samples obtained 11, 25, and 48 months prior ...

The regulation of T cell-dendritic cell (DC) contacts during clonal expansion is poorly defined. Although optimal CD4 T cell responses require prolonged exposure to antigen (Ag), it is believed that stable T cell-DC interactions occur only during the first day of the activation process. Here we show that recently activated CD4 T cells are in fact fully competent for establishing contact with Ag...

The induction of bystander suppression, whereby the response against one Ag is suppressed when it is presented in the context of an Ag to which tolerance is already established, would be an important property of oral tolerance, because it would allow treatment of autoimmune and hypersensitivity responses where the initiating Ag is not known. Although bystander suppression has been described in ...

OBJECTIVE Few studies have specifically examined proviral load (PVL) and clonal evolution of human T-lymphotropic virus type 1 (HTLV-1)-infected cells in vertically infected children. METHODS Sequential samples (from ages 1 to 16 years) from 3 HTLV-1-infected children (cases A, B and C) in the Jamaica Mother Infant Cohort Study were analyzed for their PVL and clonal expansion of HTLV-1-infect...

The costimulatory receptor OX40 has recently been shown to be involved in primary CD4 responses to several defined Ags. However, to date there has been little information regarding the mechanism of action of OX40, such as whether it regulates T cell numbers, reactivity, or both, and whether it contributes to induction of long-term T cell responses. With an agonist Ab to OX40, and by tracking Ag...

CD4(+) T cells respond to antigen immunization through a process of activation, clonal expansion to generate activated effector T cells followed by activation-induced clonal deletion of the responding T cells. While loss of responding T cells in post-activation death by apoptosis is a major factor regulating immune homeostasis, the precise pathways involved in downsizing of Plasmodium falciparu...

We have demonstrated Th2 clonal anergy as a consequence of partial T cell activation by immunogenic peptide and chemically fixed APC, as well as by altered peptide ligand and live antigen-presenting cells (APC). Either stimulation resulted in a profound inability of the T cells to proliferate upon restimulation with antigen and functional APC, a similar phenomenon to that found with Th1 cells. ...

A detailed understanding of the effects of costimulatory signals on primary T cell expansion has been limited by experimental approaches that measure the bulk response of a cell population, without distinguishing responses of individual cells. Here, we have labeled live T cells in vitro with a stable, fluorescent dye that segregates equally between daughter cells upon cell division, allowing th...

The clonal expansion of mutant cells is hypothesized to be an important first step in cancer formation. To understand the earliest stages of tumorigenesis, a method to identify and analyze clonal expansion is needed. We have previously described transgenic Fluorescent Yellow Direct Repeat (FYDR) mice in which cells that have undergone sequence rearrangements (via homologous recombination events...