Rejection of organs and other tissue is common. It's hard to find a good match, and usually people who receive tissue donations have to take immune suppressants.
And yet, there seem to be a lot of tetragametic chimeras, far more than people once believed. What prevents the cell lines from rejecting each other?
For the same reasons that your body doesn't normally reject itself.
The adaptive immune system does not have an inbuilt program that tells it what's self and what's foreign. It has to learn it. This process is called "education". In brief, the developing lymphocytes migrate to the thymus, where they encounter a sampling of antigens from the body's peripheral tissues. If they bind any of it, they're either killed or become regulatory lymphocytes. Only the ones that can't bind any of what they see in the thymus are released into the circulation as cytotoxic effectors, to see if they bind any non-self sequence, especially when they encounter one in the context of tissue damage or pathogen-associated molecular signatures.
The antigens on your chimeric cells are with you from conception. They would be fed into the thymic education process like any self antigen. And so your lymphocyte sets would become tolerant towards them just like they are tolerant towards any other antigen that floats around in your developing body in the absence of danger signals. I can't see anything "special" that would set the antigens from chimeric cells apart during the education process.
I kind of figured. Adaptive immunity takes a while to develop, so if the cells are there from the beginning, it learns that it is "self" rather than "not self." This idea should hold true for a rather weird situation where you have heteropaternal superfecundation along with tetragametic chimeras then. Okay, so having different fathers shouldn't make it impossible, or even reduce the chances of the cell lines working together.
I got bored and started thinking about whether three parent offspring in nature could even be a thing in humans. I think it can, and I'd be surprised if there aren't such people walking around without realizing it. https://medium.com/the-spiritual-anthropologist/is-it-possible-for-a-child-to-have-three-parents-ef7f1650c4f0?source=friends_link&sk=386ee87b00eba65195b0ca00c457451e
Any antigens present during the period of lymphoid development are exposed to the immune system so the immune system learns to identify and recognise these as "Self", this is the basis of immune tolerance. This includes "chimeric" or more accurately in a genetic context, the antigens of "mosaic" cell populations.
Any antigen which is not introduced at this time will later be identified as foreign - this applies to some of our own antigens that are not recipients of the immune tolerance process, these "sequestered" antigens include those from the lens of the eye and the sperm, so if these are exposed to the immune system later in life, there will be an immune response mounted against them (anti-sperm antibodies are a cause of secondary infertility).
TLDR: If it wasn't there to start with, it will (likely) be rejected.
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