The fate of adoptively transferred antigen-specific T cells in vivo.

Abstract

In this study, anti-major histocompatibility complex class I Ld T cell receptor (TCR)-transgenic cells were adoptively transferred into severe-combined immunodeficient (Scid) mice which express the Ld Ag on all nucleated cells, and the fate of transferred antigen-specific T cells (ASTC) was followed in vivo. It was found that, after encountering antigen (Ag) in vivo, the number of ASTC increased 10-15-fold followed by a decline in number to a value that was still above the starting value. The expansion of ASTC could be abrogated by blocking CD28 on the T cells prior to Ag stimulation. Using the technique which simultaneously stains ASTC surface markers and apoptotic cells, we have not only demonstrated directly that the ASTC that disappeared from the periphery died by activation-induced apoptosis but also studied their kinetics in vivo. The remaining ASTC moderately down-regulated both TCR and CD8 on their cell surface and were fully unresponsive when cultured with Ld+ cells even in the presence of exogenous interleukin (IL)-2 and IL-4. However, they were still susceptible to apoptosis when transferred into a secondary host that provided a new source of Ag and antigen-presenting cells. These studies indicate that peripheral T cell tolerance can be induced by multiple mechanisms in which activation-induced ASTC apoptosis plays an important role.