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Immune reconstitution following hematopoietic stem-cell transplantation

https://doi.org/10.1016/j.beha.2006.09.009Get rights and content

Hematopoietic stem-cell transplantation is associated with a profound immune deficiency manifested as an increased propensity to develop infections and probably also malignancies. Innate immunity, including epithelial barriers and phagocytes, typically recovers within weeks after grafting, and B-cell counts and CD8 T-cell counts recover within months. CD4 T-cell counts are low for years, and their recovery is particularly slow in older patients with poor thymic function. Therapies to improve immune function include vaccinations, immunoglobulins for recurrent infections, cytokines, and antigen-specific donor lymphocyte infusions.

Section snippets

Barrier immunity

Within the respiratory, gastrointestinal and urogenital tracts and on the skin, intact epithelium provides a physical barrier preventing translocation of bacteria and infection. Secretions like tears or saliva that contain antimicrobial molecules (including lysozyme) further facilitate this barrier function.14 Chemotherapy, radiation therapy and GVHD cause mucosal damage and skin damage. Mucosal damage is typically repaired within several weeks, except in the presence of GVHD which is

T-lymphocyte number and function

T-lymphocyte function is essential for cell-mediated immunity protective against fungal, viral, and protozoan infections, and for control of B-lymphocyte responses to encapsulated bacteria. The number of mature T cells infused during transplantation is 1 to 1.5 log higher when allogeneic stem cells are obtained from blood than marrow.*21, 40, 41 Cord blood contains fewer T cells than a typical adult marrow graft, and has a high naïve:memory/effector T-cell ratio.42, 43

CD8 cell counts recover

Non-myeloablative transplantation

Non-myeloablative transplants use non-intensive chemoradiation, relying on graft antineoplastic activity to treat the underlying disease. Some non-myeloablative conditioning regimens include anti-T-cell antibodies. Non-myeloablative transplants are increasingly used in patients with comorbidities or increased age in an attempt to reduce treatment-related mortality, and result in decreased damage to mucosal and dermal barriers. In comparison to myeloablative transplantation, reduced-intensity

Pathogen avoidance

During the neutropenic period regular hand-washing, isolation of hospitalized patients with resistant organisms to prevent spread, and the use of high-efficiency particulate air (HEPA) filters on hospital units as well as avoidance of ill contacts are important in avoiding infection.90, 91 A diet avoiding unwashed fruits and vegetables, uncooked meats and unpasteurized dairy products may prevent exposure to environmental and food-borne pathogens; the impact on infection rates of strict

Summary

Immune reconstitution following allogeneic transplant involves all aspects of innate and adaptive immunity. Breakdown of barrier immunity due to chemoradiation or GVHD is repaired, and donor cells rapidly replace phagocytes. With myeloablative transplants, there is rapid reconstitution of B lymphocytes and CD8 T lymphocytes over months, with recapitulation of B-cell ontogeny, but CD8 T cells adopt a phenotype consistent with antigen-primed rather than naïve cells. CD4 T-lymphocyte recovery is

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