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Review
. 2002 Feb;109(3):295-9.
doi: 10.1172/JCI14941.

Activation and inhibition of lymphocytes by costimulation

Kenneth A Frauwirth  1 , Craig B Thompson
Affiliations
Review

Activation and inhibition of lymphocytes by costimulation

Kenneth A Frauwirth et al. J Clin Invest. 2002 Feb.
No abstract available

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Figures

Figure 1
Figure 1
Costimulation involves reciprocal and sequential signals between cells. A T cell–APC interaction begins when the T cell antigen receptor is stimulated by a specific peptide/MHC complex on the surface of the APC (not shown). Low constitutive levels of B7.1 and/or B7.2 on the APC activate CD28 on the T cell, inducing upregulation of CD40L. CD40L in turn binds to CD40 on the APC, enhancing B7.1/B7.2 expression and reinforcing the CD28/CD40 positive feedback loop. CD28 costimulation also induces T cell expression of ICOS, allowing a second level of costimulation by APC-expressed ICOSL. Other costimulatory and inhibitory molecules regulated by the initial costimulatory signals (not shown) can further shape the specific outcome of the interaction.
Figure 2
Figure 2
Pathways implicated in CD28 signaling. Cross-linking of CD28 induces tyrosine phosphorylation of the cytoplasmic tail, allowing interaction with Grb2 and PI3K (although both are portrayed interacting with a single CD28 dimer, it is unknown whether this is a physiological complex). Grb2 links via SLP-76 to the Rho family guanine-nucleotide exchange factor Vav, connecting CD28 to activation of Rac and CDC42. PI3K can signal by recruiting Akt. Negative regulation of Vav by Cbl-b and of Akt by PP2A opposes CD28 costimulatory signals.
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