Figure 4: A schematic representation of nTreg cellimmunosuppression by cAMP following gp120 ligation of CD4(adopted from Tasken, K. 2009 [47]). Upon triggering of CD4 onTregs by gp120 protein or possibly gp120-derived agonists, Lckbecomes active and turns on cAMP production by adenylyl cyclasepossibly through interaction with a G protein [68]. cAMP istransferred from Tregs to Tcons through cell-to-cell contacts calledgap junctions that allow diffusion of small molecules down theconcentration gradient and into Tcons [49]. Once inside effectorcells, cAMP inhibits immune function through PKA-Csk inhibitorypathway that turns off T-cell activation proximally under the T-cellReceptor (TCR) in parallel with induction of potent inhibitor ofcAMP-mediated transcription ICER (inducible cAMP earlyrepressor) leading to transcriptional attenuation of IL-2 andnumerous other NFAT-driven cytokines and chemokines[44,54,71,72]. This could ameliorate Graft Versus Host Disease(GvHD) and lead to reduced tissue rejection and/or autoimmunity[67,73]