Clinical and basic scientific implications of cell migration and microchimerism after organ transplantation.

Whole organ transplantation practices have text to exploit basic immunologic information in xebrought this form of surgical treatment to a high no transplantation and other initiatives, level of efficiency and success, contrary to the pesThis 2-way (bidirectional) paradigm has been unsimistic predictions at the outset of most immunoloder intense examination because it has mandated regists. Historically, an allograft was envisioned as deexamination of transplantation immunology at every fenseless and vulnerable to immunologic attack in level. First, the 2-way paradigm established the long proportion to its histocompatibility disparity with sought linkage between the whole organ transplant that of the recipient. This dogma defined transplanpractices that were evolved empirically and the tation in terms of a unidirectional immune reaction neonatal acquired immunologic tolerance originally both for bone marrow and organs (a one-way paradescribed more than 40 years ago by Billingham, digm) (Fig. 1). Brent, and Medawar (7,8). The discoveries of sponThe one-way paradigm was unchallenged for more taneous chimerism gave startling insight into what than 3 decades until in 1992, we discovered the preswas actually being accomplished with whole organ ence of ubiquitous low level donor leukocyte chimetransplantation, allowing a revision of historic conrism in our human organ recipients as long as 30 text. years posttransplantation (1,2). We postulated from More importantly, these discoveries have illumithese findings (and subsequently obtained much nated the future (9). The mechanisms leading to confirmatory evidence [3-5]) that the interaction of chimerism and governing allograft acceptance also 2 coexisting donor and recipient leukocyte populaultimately determine the outcome after xenotranstions, each to the other, was the generic mechanism plantation. Although it will be difficult to first breech of successful tolerance after bone marrow transplanthe humoral barrier, manipulating the individual tation as well as the acceptance of organ allografts limbs of the 2-way reaction (host versus graft and (Fig. 2). graft versus host) is expected to be the key to The phenomenology of microchimerism has been the ultimate successful use of animal organs in huwidely verified in experimental models. The mutual mans. cancelling effect of the coexisting cell populations explains the blurring of a major histocompatibility complex (MHC) matching effect on the outcome of organ transplantation, the ability to transplant his toincompatible liver, intestine, and bone marrow to the noncytoablated recipient without causing graftversus-host disease (GVHD), and the ability to stop immunosuppression in many organ recipients (1,2,6). Most importantly, this concept provides a fresh con-