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Abstract
The encounter with different environmental antigens during immune maturation from childhood through early adulthood could play a role in the development of autoimmune disease in individuals with a susceptible genetic background. Autologous haematopoietic stem cell transplantation (HSCT) is an experimental treatment for autoimmunity that could offer a second possibility to correct for an aberrant immune reactivity. The premise is that eradication of the existing and pathogenic immune repertoire, in combination with the reinfusion of precursor cells, could reset the immunological clock to an earlier, latent phase of disease. Re-education of the adaptive immune system would occur during the reconstitution of cells under extreme lymphopenia, in which the antigenic priming takes place with a different sequence and timing than during the previous immunological history of the individual, resulting in a different immune repertoire. In this article, we discuss different mechanisms that could contribute to the development of tolerance during immune re-education and address the role of immune renewal and the qualitative reshaping of immunological memory.
Acknowledgements
Our understanding of the mechanisms of hematopoietic transplantation is based on the work of many clinicians and scientists who have made relevant contributions to the field. We apologise to those Authors whose work could not be discussed here due to space limitations. We also thank the patients who donated blood specimens for research. This work was funded in part by a grant from the Hammersmith Hospitals Trustees' Research Committee (to P.A.M.; number 70159).
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.