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Additional info for Annual Review of Immunology Volume 23 2005
In support of this idea, Myers et al. (223) found that anti-4-1BB stimulation of adoptively transferred CD8 T cells in the presence of Toll-receptor triggering (LPS) resulted in profound expansion of CD8 T cells, which in turn led to suppression of CD4 T cell proliferation by a TGF-β-dependent mechanism. Follow-up experiments also show that this effect is Ag-specific and IFN-γ -dependent (L. Myers & A. Vella, manuscript in preparation). The finding that anti-4-1BB can have apparently inhibitory or stimulatory effects depending on the disease and/or level of immune response means that one should exercise caution in applying anti-4-1BB therapeutically.
For personal use only. TNF FAMILY MEMBERS AS COSTIMULATORS 31 in vitro activation, declining again between 72 and 96 hr (104). Although CD28 is not essential for OX40 expression, engagement of CD28 can enhance the kinetics and level of OX40 expression on T cells (54, 105). OX40 is preferentially expressed on Th2 cells in some models (106, 107), but it can also be expressed on Th1 cells (104, 107, 108) and can play a role in both Th1 and Th2 responses (to be discussed below). In vivo, OX40-expressing CD4 T cells are found in close proximity to antigen-activated B cells in the spleen (107, 109).
Costimulatory effects of LIGHT on purified T cells are independent of CD28 signaling (246). Blocking of HVEM-LIGHT interaction using HSV-1 glycoprotein D, antiHVEM, or HVEM-Ig inhibits the proliferation of purified T cells responding to anti-CD3 or anti-CD3/CD28 (248–250). Furthermore, two studies showed that purified LIGHT–/– T cells have decreased responses to anti-CD3 alone, consistent with HVEM-LIGHT interactions during T-T interaction enhancing proliferation (251, 252). Although a third study did not show any defect in proliferation of LIGHT−/− T cells (253), this may reflect lower cell densities in the cultures leading to less efficient T-T contact.
Annual Review of Immunology Volume 23 2005 by Annual Reviews