CD28 ligands CD80 (B7-1) and CD86 (B7-2) induce long-term autocrine growth of CD4+ T cells and induce similar patterns of cytokine secretion in vitro |
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Authors: | Levine Bruce L; Ueda Yuji; Craighead Nancy; Huang Mark L; June Carl H |
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Institution: | 1 Immune Cell Biology Program, Naval Medical Research Institute Bethesda, MD 20889, USA
2 Department of Medicine, Uniformed Services University of the Health Sciences Bethesda, MD 20889, USA
3 Geo-Centers Inc. Fort Washington, MD 20744, USA |
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Abstract: | The interaction of CD28 and its ligands is critical for antigen-inducedT cell activation. Recent studies have demonstrated the existenceof at least two members of the B7 receptor family. In this report,the co-stimulatory signals provided by CD80 (B7-1) or CD86 (B7-2)were compared to CD28 ligation by mAb. We demonstrate that thekinetics of induction of T cell proliferation after anti-CD3stimulation was similar regardless of the form of co-stimulation.Similarly, B7-1 and B7-2 could both maintain long-term expansionof CD4 cells. The co-stimulatory effects of both B7-1 and B7-2were dependent on CD28 cross-linking, based on complete inhibitionof proliferation by CD28 antibody Fab fragments. Co-stimulationwith B7-1 and B7-2 induced high levels of cytokine secretionby resting T cells, and the effects of B7-1 and B7-2 could notbe distinguished. This conclusion is based on analysis of theinitial activation of CD28+ T cells. as well as T cell subpopulationsconsisting of CD4+ and CD8+ T cells. Both B7-1 and B7-2 couldelicit IL-4 secretion from CD4+ T cells while anti-CD28 antibodyinduced substantially less IL-4 secretion. Furthermore, bothB7-1 and B7-2 could stimulate high levels of IFN- and IL-4 fromCD4+CD45RO+ cells, while neither B7 receptor could co-stimulateIFN- and IL-4 secretion from CD4+CD45RA+ T cells. B7-1 and B7-2could, however, co-stimulate CD4+CD45RA+ T cells to secreteIL-2. By contrast, when previously activated T cells were tested,re-stimulation of CD4+ T cell blasts with B7-1 or B7-2 resultedin higher secretion of IL-4 and IL-5 than anti-CD28, while re-stimulationwith anti-CD28 antibody maintained a higher level of secretionof IL-2 and IFN- than B7-1 or B7-2. These observations may haveimportant implications because they suggest that the mannerof CD28 ligation can be a critical determinant in the developmentof cytokine secretion that corresponds to Th1- and Th2-likepatterns of differentiation. Together these observations suggestthat there are no Intrinsic differences between B7-1 and B7-2in their ability to co-stimulate the populations of cells thatwe have tested. |
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Keywords: | B7 CD28 CD80 CD86 co-stimulation cytokine T helper |
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