title: Profound CD4+/CCR5+ T cell expansion is induced by CD8+ lymphocyte depletion but does not account for accelerated SIV pathogenesis.
abstract: Depletion of CD8(+) lymphocytes during acute simian immunodeficiency virus (SIV) infection of rhesus macaques (RMs) results in irreversible prolongation of peak-level viral replication and rapid disease progression, consistent with a major role for CD8(+) lymphocytes in determining postacute-phase viral replication set points. However, we report that CD8(+) lymphocyte depletion is also associated with a dramatic induction of proliferation among CD4(+) effector memory T (T(EM)) cells and, to a lesser extent, transitional memory T (T(TrM)) cells, raising the question of whether an increased availability of optimal (activated/proliferating), CD4(+)/CCR5(+) SIV "target" cells contributes to this accelerated pathogenesis. In keeping with this, depletion of CD8(+) lymphocytes in SIV(-) RMs led to a sustained increase in the number of potential CD4(+) SIV targets, whereas such depletion in acute SIV infection led to increased target cell consumption. However, we found that the excess CD4(+) T(EM) cell proliferation of CD8(+) lymphocyte-depleted, acutely SIV-infected RMs was completely inhibited by interleukin (IL)-15 neutralization, and that this inhibition did not abrogate the rapidly progressive infection in these RMs. Moreover, although administration of IL-15 during acute infection induced robust CD4(+) T(EM) and T(TrM) cell proliferation, it did not recapitulate the viral dynamics of CD8(+) lymphocyte depletion. These data suggest that CD8(+) lymphocyte function has a larger impact on the outcome of acute SIV infection than the number and/or activation status of target cells available for infection and viral production.
authors: Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR 97006, USA.
authors: Afam
authors: A
authors: Okoye
authors: Haesun
authors: H
authors: Park
authors: Mukta
authors: M
authors: Rohankhedkar
authors: Lia
authors: L
authors: Coyne-Johnson
authors: Richard
authors: R
authors: Lum
authors: Joshua M
authors: JM
authors: Walker
authors: Shannon L
authors: SL
authors: Planer
authors: Alfred W
authors: AW
authors: Legasse
authors: Andrew W
authors: AW
authors: Sylwester
authors: Michael
authors: M
authors: Piatak
authors: Jeffrey D
authors: JD
authors: Lifson
authors: Donald L
authors: DL
authors: Sodora
authors: Francois
authors: F
authors: Villinger
authors: Michael K
authors: MK
authors: Axthelm
authors: Joern E
authors: JE
authors: Schmitz
authors: Louis J
authors: LJ
authors: Picker
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000821:virology*; D049109:Cell Proliferation; D007156:Immunologic Memory / Q000276:immunology; D019409:Interleukin-15 / Q000097:blood / Q000235:genetics / Q000276:immunology; D008212:Lymphocyte Depletion; D008253:Macaca mulatta / Q000276:immunology / Q000821:virology; D008297:Male; D019713:Receptors, CCR5 / Q000276:immunology*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000473:pathology / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology / Q000472:pathogenicity; D015996:Survival Rate; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000821:virology*; D014779:Virus Replication
chemical_list: D000914:Antibodies, Viral; D019409:Interleukin-15; D019713:Receptors, CCR5; D011994:Recombinant Proteins