Propagation and characterization of lymphocytes from transplant biopsies

This review shows that the propagation and characterization of lymphocytes from various solid organ allografts leads to a better understanding of cellular transplant immunity. Clinically relevant information generated by many studies offers opportunities for better management of transplant patients for cellular rejection. These studies provide experimental support of the importance of various class I and class II HLA antigens in cellular rejection, and frequently the population of infiltrating alloreactive T cells is clonally restricted. Evidence has also accumulated that class I-specific CD8+ cells often appear first in the allograft undergoing early rejection. Allograft derived lymphocytes can also be used in in vitro models to study interactions with vascular endothelium and other targets of cellular rejection. Studies on biopsy propagated cells have also increased our understanding of chronic rejection and intragraft tolerance. Nevertheless, many unanswered questions remain which need to be addressed in future studies. This particularly applies to the mechanism of intragraft T-cell clonality and the characterization of cells mediating chronic rejection or transplant tolerance. A major area of investigation needed over the next few years should address the role of cytokines in the complex interactions between cells mediating the inflammatory process during allograft rejection and the mechanisms of donor tissue injury. This can be done by determining cytokine release by allograft derived cell cultures and by applying molecular techniques to measure in situ production of cytokines in allograft tissue specimens. Given the plethora of cytokines identified so far (the list is still growing), it would be difficult to determine the functional role of individual cytokines in the inflammatory process. Most cytokines have been ascribed multiple functions and for several, their activity requires a synergism with other cytokines or immune modulators. The biological significance of cytokine function must be assessed at different phases during the cascade of effector mechanisms leading to cellular rejection. The first phase pertains to the interactions between lymphocytes and the vascular endothelium. Major events include lymphocyte adhesion to the EC, specific allorecognition, and cellular activation. A variety of cytokines have been identified which upregulate the expression of adhesion molecules and HLA alloantigens at the cell surface. This augments the activated state of the adhering T cells and also triggers the endothelium to attract other leukocytes and permit diapedesis of adhering cells. Although at least four systems of interrelated adhesion receptor-ligand combinations have been shown to influence lymphocyte-endothelium interactions, it is unclear how much each contributes to the process of lymphocyte infiltration through the vascular endothelial barrier.(ABSTRACT TRUNCATED AT 400 WORDS)