Impaired T-cell differentiation in the thymus at the early stages of acute pathogenic chimeric simian-human immunodeficiency virus (SHIV) infection in contrast to less pathogenic SHIV infection.
One of the mechanisms by which HIV infection induces the depletion of CD4+ T cells has been suggested to be impairment of T-cell development in the thymus, although there is no direct evidence that this occurs. To examine this possibility, we compared T-cell maturation in the intrathymic progenitors between macaques infected with an acute pathogenic chimeric simian-human immunodeficiency virus (SHIV), which causes profound and irreversible CD4+ T-cell depletion, and macaques infected with a less pathogenic SHIV, which causes only a transient CD4+ T-cell decline. Within 27 days post-inoculation (dpi), the two virus infections caused similar increases in plasma viral loads and similar decreases in CD4+ T-cell counts. However, in the thymus, the acute pathogenic SHIV resulted in increased thymic involution, atrophy and the depletion of immature T cells including CD4(+)CD8(+) double-positive (DP) cells, whereas the less pathogenic SHIV did not have these effects. Ex vivo differentiation of CD3(-)CD4(-)CD8(-) triple-negative (TN) intrathymic progenitors to DP cells was assessed by a monkey-mouse xenogenic fetal thymus organ culture system. Differentiation was impaired in the TN intrathymic progenitors of the acute pathogenic SHIV-infected monkeys, while differentiation was not impaired in the TN intrathymic progenitors of the less pathogenic SHIV-infected monkeys. These differences suggest that dysfunction of thymic maturation makes an important contribution to the irreversible depletion of circulating CD4+ T cells in vivo.
Motohara
Makiko
M
Laboratory of Primate Model, Experimental Research Center for Infectious Diseases, Institute for Virus Research, Kyoto University, 53 Shogoinkawara-Machi, Sakyo-Ku, Kyoto 606-8507, Japan.
Ibuki
Kentaro
K
Miyake
Ariko
A
Fukazawa
Yoshinori
Y
Inaba
Katsuhisa
K
Suzuki
Hajime
H
Masuda
Kyoko
K
Minato
Nagahiro
N
Kawamoto
Hiroshi
H
Nakasone
Tadashi
T
Honda
Mitsuo
M
Hayami
Masanori
M
Miura
Tomoyuki
T
D000818:Animals; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002454:Cell Differentiation / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006678:HIV / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008253:Macaca mulatta; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D013234:Stem Cells / Q000276:immunology / Q000821:virology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology* / Q000821:virology*; D019562:Viral Load
D012367:RNA, Viral