Simian immunodeficiency virus selectively infects proliferating CD4+ T cells in neonatal rhesus macaques.
Infants infected with HIV have a more severe course of disease and persistently higher viral loads than HIV-infected adults. However, the underlying pathogenesis of this exacerbation remains obscure. Here we compared the rate of CD4(+) and CD8(+) T-cell proliferation in intestinal and systemic lymphoid tissues of neonatal and adult rhesus macaques, and of normal and age-matched simian immunodeficiency virus (SIV)-infected neonates. The results demonstrate infant primates have much greater rates of CD4(+) T-cell proliferation than adult macaques, and that these proliferating, recently "activated" CD4(+) T cells are infected in intestinal and other lymphoid tissues of neonates, resulting in selective depletion of proliferating CD4(+) T cells in acute infection. This depletion is accompanied by a marked increase in CD8(+) T-cell activation and production, particularly in the intestinal tract. The data indicate intestinal CD4(+) T cells of infant primates have a markedly accelerated rate of proliferation and maturation resulting in more rapid and sustained production of optimal target cells (activated memory CD4(+) T cells), which may explain the sustained "peak" viremia characteristic of pediatric HIV infection. Eventual failure of CD4(+) T-cell turnover in intestinal tissues may indicate a poorer prognosis for HIV-infected infants.
Wang
Xiaolei
X
Tulane National Primate Research Center, Tulane University School of Medicine, Covington, LA, USA.
Xu
Huanbin
H
Pahar
Bapi
B
Alvarez
Xavier
X
Green
Linda C
LC
Dufour
Jason
J
Moroney-Rasmussen
Terri
T
Lackner
Andrew A
AA
Veazey
Ronald S
RS
D000375:Aging / Q000276:immunology; D000818:Animals; D000831:Animals, Newborn; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000821:virology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000821:virology; D049109:Cell Proliferation; D007150:Immunohistochemistry; D016130:Immunophenotyping; D017403:In Situ Hybridization; D008212:Lymphocyte Depletion; D016131:Lymphocyte Subsets / Q000166:cytology / Q000821:virology; D008253:Macaca mulatta / Q000276:immunology* / Q000821:virology*; D009928:Organ Specificity / Q000276:immunology; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D016097:Simian Acquired Immunodeficiency Syndrome / Q000097:blood / Q000150:complications / Q000276:immunology* / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D019562:Viral Load / Q000276:immunology; D014766:Viremia / Q000097:blood / Q000150:complications / Q000276:immunology
D012367:RNA, Viral