What makes you think the US even has the resources and manpower to 'lock down' all major US cities- at least in any effective way, even assuming there was some logical reason to 'lock down' cities in the first place? For example, about the only reason could be a biological attack using not anthrax, but some TRANSMISSIBLE agent like smallpox)
This country is enormous- few people realize just how immense this country is. Not only is it enormous, but the geography and infrastructure would not work in the favor of any effort to isolate specific regions.
Major American cities even by themselves are enormous and cannot be efficiently cordoned off, unless everyone concerned is willing to abide by the rules, and when has that ever happened? Perhaps isolating a city like Las Vegas would be prectical, but try to isolate a city such as St. Louis, Memphis or Chicago without the full cooperation of the residents and the effort would fail miserably.
Were there a biological attack, and locking down areas were thus made neccessary to limit the spread, there would be no logical reason to break travel restrictions, unless of course you want to help spread transmissible agents outside the lockout zone. Oh, certainly some people would try. And some would likely succeed.
I remember the flood of 93 where most people cooperated in dealing with the situation and volunteers came from all over, frequently unasked, to help shore up levees against rising waters, to provide medical aid, bring in supplies, to secure areas against possible looters, and even to clean up afterwards. (We had to arm ourselves to protect the state's water pumps and our neighbors' pumps from occasional aggressive thieves desperate to obtain them to save their own property or planning to sell hot pumps to those who were unable to buy them legally.)
There are always going to be people who care only about themselves, such as the guy who took his boat out to try to ram already saturated levees in an effort to save his fields. But when things come down to the wire, the bulk of people work together to do what is neccessary, just as in the flood of 93, or in Gulf coast hurricanes, or in harsh winter storms, western firestorms, etc, and have the resources stashed away to live independently and make things happen when neccessary. They will be able to apply these same resources and resourcefulness they use in natural disasters to situations which are decidedly 'unnatural.'