The T cell response to an organ graft may be initiated in the lymph nodes that drain the graft (Fig. 16-6). Most organs contain resident APCs such as dendritic cells. Transplantation of these organs into an allogeneic recipient provides APCs that express donor MHC molecules as well as costimulators. It is believed that these donor APCs migrate to regional lymph nodes and present, on their surface, unprocessed allogeneic MHC molecules to the recipient's T cells (the direct pathway of allorecognition). Host dendritic cells from the recipient may also migrate into the graft, pick up graft alloantigens, and transport these back to the draining lymph nodes, where they are displayed (the indirect pathway). Naive lymphocytes that normally traffic through the lymph node encounter these alloantigens and are induced to proliferate and differentiate into effector cells. This process is sometimes called sensitization to alloantigens. Effector T cells migrate back into the graft and mediate rejection.
As many as 1% to 2% of an individual's T cells are capable of recognizing and responding to a single foreign MHC molecule, and this high frequency of T cells reactive with allogeneic MHC molecules is one reason that allografts elicit strong immune responses. Recall that the frequency of T cells reactive with any foreign (e.g., microbial) antigen is only 1 in 105 or 106. The likely reasons that each allogeneic MHC molecule is directly recognized by so many different TCRs were discussed earlier.
Many of the T cells that respond to an allogeneic MHC molecule, even on first exposure, are memory T cells. It is likely that these memory cells were generated during previous exposure to other foreign (e.g., microbial) antigens and cross-react with allogeneic MHC molecules. These memory cells are not only expanded populations of antigen-specific cells but also more rapid and powerful responders than naive lymphocytes, and thus contribute to the strength of the alloreactive T cell response. Memory cells are also thought to be more resistant to immunosup-pression than are naive lymphocytes, and the presence of large numbers of memory cells may lead to poor outcomes of transplantation.
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