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Title: Lymphocyte homeostasis and autoimmunity following therapeutic lymphocyte depletion in the treatment of multiple sclerosis
Author: Cox, A. L.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2006
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Campath-1H induces immediate lymphocyte depletion and remission of inflammatory disease activity when used to treat multiple sclerosis. A cohort of 16 people with multiple sclerosis were studied for one year following a single pulse of Campath-1H treatment. In addition to reporting on their clinical course, serial detailed immunological investigations were performed focusing on immunoregulation and homeostasis. Two phases of lymphocyte reconstitution following Campath-1H treatment were observed. In the first six months lymphocyte proliferation increased and the residual T cell pool was dominated by memory T cells, especially regulatory T cells. In the later phase these changes reversed. The relative fall in regulatory T cell numbers coincided with a period of susceptibility to novel autoimmunity offering a mechanism by which proliferating auto-reactive T cells might escape control. Total CD4+ numbers remained below 50% of pre-treatment levels at twelve months despite a sustained increase in IL-7. However CCL21 and Il-15 responses to lymphopaenia appear to be suboptimal explaining the delayed lymphocyte reconstitution. Auto-reactive lymphocytes exist in the normal T Cell repertoire. As exposure to myelin antigens may result in autoimmune type activation of T cells, lymphocyte responses were investigated in 10 head injury patients. Proliferation and cytokine production following ex vivo exposure to myeline protein was generally suppressed. However, some individuals demonstrated increased reactivity and reduced TGF-b expression suggesting relatively less regulation of auto-reactivity.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available