TY - JOUR
T1 - 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
AU - Motohara, Makiko
AU - Ibuki, Kentaro
AU - Miyake, Ariko
AU - Fukazawa, Yoshinori
AU - Inaba, Katsuhisa
AU - Suzuki, Hajime
AU - Masuda, Kyoko
AU - Minato, Nagahiro
AU - Kawamoto, Hiroshi
AU - Nakasone, Tadashi
AU - Honda, Mitsuo
AU - Hayami, Masanori
AU - Miura, Tomoyuki
N1 - Funding Information:
We are grateful to James Raymond for proofreading this manuscript, to Yoko Isamoto, Kyoko Yokoyama, Becton Dickinson and DAKO Corp. for technical support. This work was supported by the Cooperation Research of Primate Research Institute, Kyoto University, a Health Sciences Research Grant from the Ministry of Health, Labour and Welfare, Japan, a Grant-in-Aid for Scientific Research from the Ministry of Education and Science, Japan and a Research Grant on Health Sciences focusing on Drug Innovation from the Japan Health Sciences Foundation. M.M. is supported by the 21st Century COE Program of the Ministry of Education, Culture, Sports, Science and Technology.
PY - 2006/5
Y1 - 2006/5
N2 - 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.
AB - 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.
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U2 - 10.1016/j.micinf.2006.01.011
DO - 10.1016/j.micinf.2006.01.011
M3 - Article
C2 - 16702011
AN - SCOPUS:33745131124
SN - 1286-4579
VL - 8
SP - 1539
EP - 1549
JO - Microbes and Infection
JF - Microbes and Infection
IS - 6
ER -