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The Proceedings of the American Thoracic Society 2:449-455 (2005)
© 2005 The American Thoracic Society

Transplant-related Immunosuppression

A Review of Immunosuppression and Pulmonary Infections

Michael D. Duncan and David S. Wilkes

Departments of Medicine, Microbiology and Immunology, and Center for Immunbiology, Indiana University School of Medicine, Indianapolis, Indiana

Correspondence and requests for reprints should be addressed to David S. Wilkes, M.D., Dr. Calvin H. English Professor of Medicine, Microbiology and Immunology Director, Center for Immunobiology, Indiana University School of Medicine, Van Nuys Medical Sciences Building MS224, 635 Barnhill Dr., Indianapolis, IN 46202-5120. E-mail: dwilkes{at}iupui.edu

ABSTRACT

Solid organ and hematopoietic stem cell transplantation are definitive therapies for a variety of end-stage diseases. Immunosuppression has improved graft survival but leaves the patient susceptible to infectious complications. Of these, pulmonary infections are the leading cause of morbidity and mortality in the transplant recipient. Allograft rejection is mediated primarily by T cells, with B cells playing a role via antibody production. Depending on the transplant type, rejection can be hyperacute, acute, or chronic. Hyperacute rejection occurs as an immediate response to preformed antibodies to donor human leukocyte antigens. Acute cellular rejection involves recipient T-cell recognition of human leukocyte antigen molecules expressed on donor-derived, antigen-presenting cells (direct allorecognition) or presentation of donor-derived peptides by recipient antigen-presenting cells to recipient T cells (indirect allorecognition). Once the alloantigens are recognized as foreign, the activation, proliferation, and production of cytokines by T lymphocytes and other immune cells lead to the amplification of the alloimmune response. This complex process involves the generation of effector T cells, antibody production by activated B cells, and macrophage activation. Alloimmunity is facilitated by the production of many cytokines, chemokines, and other effector molecules, such as complement. The immunosuppressants involve many classes of drugs, including antibody therapies that eliminate specific groups of cells or alter signaling pathways used by effector cells. The article reviews the agents and associated infections.

Key Words: hematopoietic stem cell transplant • immunosuppression and pulmonary infections • solid organ transplant






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