e450 tranny temps

Mine generally stays about 90F above ambient when I'm towing.

If your E450 is stock and you stay within the rating, you probably have nothing to worry about. The hottest trans temps I ever see are actually doing things like backing a trailer up a driveway after getting off the freeway. Towing on the highway, even in the mountains, is never a problem.

But it is still a good idea to monitor. I have a Banks trans temp gauge mounted in my A-pillar. You can also plug something in like the ScanGauge-2 which monitors the data stream through your OBD2 port.

Mine stays at 180F in 105F ambient temps while driving in the hills pulling a bike trailer.

IMHO gauges are a must.
By the time a warning alerts you, it's too late.

No gauges at all means you have no idea what's going on.
Knowing what the optimal temps are is of no benefit you you since you don't have gauges.

Trans and engine coolant temps aren't really related. You can cook your tranny fluid without coming close to overheating your engine.

I think the overdrive light will blink AFTER it gets hot.