The influence of costimulation on the primary response of CD8+ T cells to class I alloantigens was studied with the aid of a T cell receptor transgenic model and defined peptides as antigen. With small doses of antigen, the proliferative response of CD8+ cells was high early in culture but was of brief duration and declined to low levels by day 4; this abbreviated response was associated with limited production of interleukin 2 (IL-2) and was strongly dependent upon costimulation via CD8-major histocompatibility complex class I and CD28-B7 interactions. The response to large doses of antigen was quite different in two respects. First, large doses of antigen inhibited the early (day 3) proliferative response but caused a marked elevation of the response late in culture (day 5); these altered kinetics were associated with increased production of IL-2. Second, the initial proliferative response to large doses of antigen did not require costimulation: indeed, blocking costimulation with CTLA4lg or anti-CD8 monoclonal antibody enhanced the early proliferative response. However, blocking costimulation impaired IL-2 production and prevented the late proliferative response. These findings indicate that the requirement for costimulation of T cells can be partly overcome by increasing the dose of antigen to a high level. However, costimulation plays a key role in prolonging the response, presumably by triggering strong and sustained production of IL-2.
Article|
May 01 1996
Influence of antigen dose and costimulation on the primary response of CD8+ T cells in vitro.
Z Cai
Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA.
J Sprent
Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1996) 183 (5): 2247–2257.
Citation
Z Cai, J Sprent; Influence of antigen dose and costimulation on the primary response of CD8+ T cells in vitro.. J Exp Med 1 May 1996; 183 (5): 2247–2257. doi: https://doi.org/10.1084/jem.183.5.2247
Download citation file: