Bone marrow-based homeostatic proliferation of mature T cells in nonhuman primates: implications for AIDS pathogenesis.
Bone marrow (BM) is the key hematopoietic organ in mammals and is involved in the homeostatic proliferation of memory CD8(+) T cells. Here we expanded on our previous observation that BM is a preferential site for T-cell proliferation in simian immunodeficiency virus (SIV)-infected sooty mangabeys (SMs) that do not progress to AIDS despite high viremia. We found high levels of mature T-cell proliferation, involving both naive and memory cells, in healthy SMs and rhesus macaques (RMs). In addition, we observed in both species that lineage-specific, BM-based T-cell proliferation follows antibody-mediated in vivo CD4(+) or CD8(+) T-cell depletion, thus indicating a role for the BM in maintaining T-cell homeostasis under depleting circumstances. We also observed that, in SIV-infected SMs, but not RMs, the level of proliferation of BM-based CD4(+) T cells is higher than that of circulating CD4(+) T cells. Interestingly, limited BM-based CD4(+) T-cell proliferation was found in SIV-infected SMs with low CD4(+) T-cell counts, suggesting a regenerative failure in these animals. Collectively, these results indicate that BM is involved in maintaining T-cell homeostasis in primates and suggest a role for BM-based CD4(+) T-cell proliferation in determining the benign nature of natural SIV infection of SMs.
Paiardini
Mirko
M
Department of Pathology & Laboratory Medicine, University of Pennsylvania, Philadelphia 19143, USA.
Cervasi
Barbara
B
Engram
Jessica C
JC
Gordon
Shari N
SN
Klatt
Nichole R
NR
Muthukumar
Alagarraju
A
Else
James
J
Mittler
Robert S
RS
Staprans
Silvija I
SI
Sodora
Donald L
DL
Silvestri
Guido
G
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D000818:Animals; D001853:Bone Marrow / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D049109:Cell Proliferation; D016665:Cercocebus atys; D005434:Flow Cytometry; D006706:Homeostasis / Q000276:immunology*; D008253:Macaca mulatta; D010641:Phenotype; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000821:virology; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology; D019562:Viral Load