| First Author | Sad S | Year | 1999 |
| Journal | J Immunol | Volume | 163 |
| Issue | 5 | Pages | 2443-51 |
| PubMed ID | 10452979 | Mgi Jnum | J:118912 |
| Mgi Id | MGI:3700631 | Doi | 10.4049/jimmunol.163.5.2443 |
| Citation | Sad S, et al. (1999) Cytokine deprivation of naive CD8+ T cells promotes minimal cell cycling but maximal cytokine synthesis and autonomous proliferation subsequently: a mechanism of self-regulation. J Immunol 163(5):2443-51 |
| abstractText | Naive CD8+ T cells differentiate into effectors secreting various cytokines that aid their function. IL-2, but not IL-15, promoted this differentiation of naive CD8+ T cells into effectors. However, the amount of IL-2 present during differentiation had a dichotomous effect on their subsequent function. High concentrations of IL-2 enhanced proliferation and cell cycling initially, but the effectors subsequently failed to produce cytokines and proliferate autonomously, although CD28 expression was maintained. In contrast, suboptimal amounts of IL-2 during priming promoted apoptosis, little proliferation and cell cycling, yet the CD8+ effectors generated produced high levels of cytokines and proliferated autonomously. Interestingly, the effects of IL-2 on naive CD8+ T cells were totally opposite those on naive CD4+ T cells. Although IL-2 impaired cytokine synthesis by CD8+ T cells, the expression of LFA1 and CD44 as well as Fas-dependent cytotoxicity were enhanced. However, loss of cytokine synthesis was not due to increased cytotoxicity, as inhibition occurred even in the absence of perforin/FasL. Interestingly, CD8+ effectors secreting reduced amounts of cytokines exhibited enhanced IL-2Ralpha, but reduced IL-2Rbeta, expression. Furthermore, sorted CD8+ IL-2Ralphahigh cells secreted less cytokines than IL-2Ralphalow cells. These results suggest that the presence of excessive IL-2 during the activation of naive CD8+ T cells, while promoting cell cycling initially, may compromise long-term immunity. |
