Lineage-specific T-cell reconstitution following in vivo CD4+ and CD8+ lymphocyte depletion in nonhuman primates.
Many features of T-cell homeostasis in primates are still unclear, thus limiting our understanding of AIDS pathogenesis, in which T-cell homeostasis is lost. Here, we performed experiments of in vivo CD4(+) or CD8(+) lymphocyte depletion in 2 nonhuman primate species, rhesus macaques (RMs) and sooty mangabeys (SMs). Whereas RMs develop AIDS after infection with simian immunodeficiency virus (SIV), SIV-infected SMs are typically AIDS-resistant. We found that, in both species, most CD4(+) or CD8(+) T cells in blood and lymph nodes were depleted after treatment with their respective antibodies. These CD4(+) and CD8(+) lymphocyte depletions were followed by a largely lineage-specific CD4(+) and CD8(+) T-cell proliferation, involving mainly memory T cells, which correlated with interleukin-7 plasma levels. Interestingly, SMs showed a faster repopulation of naive CD4(+) T cells than RMs. In addition, in both species CD8(+) T-cell repopulation was faster than that of CD4(+) T cells, with CD8(+) T cells reconstituting a normal pool within 60 days and CD4(+) T cells remaining below baseline levels up to day 180 after depletion. While this study revealed subtle differences in CD4(+) T-cell repopulation in an AIDS-sensitive versus an AIDS-resistant species, such differences may have particular relevance in the presence of active SIV repli cation, where CD4(+) T-cell destruction is chronic.
Engram
Jessica C
JC
Department of Pathology, University of Pennsylvania, Philadelphia, USA.
Cervasi
Barbara
B
Borghans
Jose A M
JA
Klatt
Nichole R
NR
Gordon
Shari N
SN
Chahroudi
Ann
A
Else
James G
JG
Mittler
Robert S
RS
Sodora
Donald L
DL
de Boer
Rob J
RJ
Brenchley
Jason M
JM
Silvestri
Guido
G
Paiardini
Mirko
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology*; D002455:Cell Division; D019070:Cell Lineage; D016665:Cercocebus atys / Q000276:immunology*; D006706:Homeostasis / Q000276:immunology; D007113:Immunity, Innate; D019409:Interleukin-15 / Q000097:blood; D015851:Interleukin-7 / Q000097:blood; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D008253:Macaca mulatta / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000276:immunology; D013045:Species Specificity; D016176:T-Lymphocyte Subsets / Q000166:cytology*
D000911:Antibodies, Monoclonal; D019409:Interleukin-15; D015851:Interleukin-7; C079851:OKT4A monoclonal antibody