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Role of co-stimulation in CD8+ T cell activation.

Abstract : The two-signal model states that activation of naive T cells requires a signal 1 stimulus through the TCR and a co-stimulatory signal 2. By contrast, signal 1 alone is sufficient for pre-activated T cells. Recently, however, it has been shown that under certain conditions T cells can bypass the requirement for co-stimulation. For example, CD28-deficient mice, when immunized with lymphocytic choriomeningitis virus, mount a vigorous cytotoxic T lymphocyte response and clear the virus. As a continuous effort to unravel the mechanisms of T cell activation, we previously reported activation of hybridoma T cells by recombinant single-chain MHC molecules in the absence of antigen-presenting cells. In such reconstitution experiments, since the signals delivered to the T cells are well controlled, the contribution of any known or unknown signals can be ruled out. In the present study, we analyzed the requirements for activation of naive T cells by using splenocytes from TCR transgenic mice as a source of responding cells. We observed that naive CD8+ T cells are fully activated by signal 1 alone, but that co-stimulation lowers their activation threshold. Previously activated T cells are fully responsive, even when the first stimulation was performed in the absence of co-stimulation. They display a low activation threshold and are insensitive to co-stimulation. The physiological relevance of this finding and its consequences for immunotherapy as well as for our understanding of self-tolerance are discussed.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-01659376
Contributor : Nathalie Pardigon <>
Submitted on : Friday, December 8, 2017 - 12:48:41 PM
Last modification on : Wednesday, October 14, 2020 - 3:48:19 AM

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N Pardigon, N. Bercovici, S Calbo, E C Santos-Lima, R. Liblau, et al.. Role of co-stimulation in CD8+ T cell activation.. International Immunology, Oxford University Press (OUP), 1998, 10 (5), pp.619-30. ⟨10.1093/intimm/10.5.619⟩. ⟨pasteur-01659376⟩

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