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Critical Reviews™ in Immunology
Th1 and Th2 Cytokines in Organ Transplantation: Paradigm Lost?
Ronald W. Busuttil
Ftafik M. Ghobrial
Jerzy W. Kupiec-Weglinski
The Dumont-UCLA Transplant Center, University of California School of Medicine, 10833 Le Conte Ave, Los Angeles, CA 90095
Identification of CD4+ T helper lymphocyte subsets that exhibit distinct cytokine elaboration patterns has provided a valuable framework for understanding the heterogeneity of the immune response. Much progress has been made in recent years in defining the cellular and molecular mechanisms by which cytokines induce T cell differentiation. In transplantation models, the Thl cytokine profile often associates with allograft rejection, while the Th2 profile favors the acquisition of tolerance. However, this paradigm may not be sufficient to explain the recently demonstrated in vivo effects of cytokine manipulation on allograft survival. Th2 cytokines may not be necessary for tolerance induction, while Thl cytokines may even be beneficial in promoting allograft survival. However, such data should be interpreted in light of the diverse and often redundant effects displayed by cytokine networks in vivo. Understanding the complex interactions of cytokines in the alloimmune cascade therefore is critical for designing therapeutic strategies that abrogate allograft rejection and induce donor-specific tolerance, an elusive goal in organ transplantation.
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