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Title: Human immunodeficiency virus infection of CD8 lymphocytes
Author: Cochrane, Alexandra
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2006
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To confirm that CD8 lymphocytes are infected with HIV in vivo, and to investigate the mechanism of infection, HIV long terminal repeat (LTR) DNA was quantified in CD8 lymphocyte subsets of known purity, isolated from the blood of 20 subjects with HIV infection. HIV LTR was demonstrated in CD8 lymphocytes of 18/20 subjects, and in the subjects with chronic infection the frequency of infection increased with disease progression. HIV infection of CD8brightCD4dim lymphocytes was significantly more frequent (median 1197 HIV LTR copies / million cells) than that of CD8+CD4- lymphocytes (undetectable in 7/9 subjects, p<0.01) suggesting infection on activation rather than during intrathymic development. The level of infection in the CD8brightCD4dim lymphocytes approached that in CD4 lymphocytes from the same subjects (median 3660 HIV LTR copies / million cells) and therefore could not be explained by CD4 lymphocyte contamination. Given the high level of infection of CD8brightCD4dim lymphocytes their prevalence and phenotype was assessed in 8 healthy and 16 HIV infected subjects. The proportion of CD8 lymphocytes with a CD8brightCD4dim phenotype ranged from 0.3 to 3.4% with no significant difference between HIV infected and healthy subjects. The majority displayed a CD45RA-ve CD27+ve (memory) phenotype, but in contrast to the populations generated in vitro, the circulating population was not uniformly activated but rather comprised both activated and quiescent cells. Thus HIV infected CD8 lymphocytes commonly circulate in HIV infected subjects, and are likely to be infected on activation rather than during intrathymic development. Given that a proportion of the circulating CD8brightCD4dim lymphocytes have a quiescent phenotype, they may act as a long lived reservoir with implications for viral eradication.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available