title: Naive T cells are dispensable for memory CD4+ T cell homeostasis in progressive simian immunodeficiency virus infection.
abstract: The development of AIDS in chronic HIV/simian immunodeficiency virus (SIV) infection has been closely linked to progressive failure of CD4(+) memory T cell (T(M)) homeostasis. CD4(+) naive T cells (T(N)) also decline in these infections, but their contribution to disease progression is less clear. We assessed the role of CD4(+) T(N) in SIV pathogenesis using rhesus macaques (RMs) selectively and permanently depleted of CD4(+) T(N) before SIV infection. CD4(+) T(N)-depleted and CD4(+) T(N)-repleted RMs were created by subjecting juvenile RMs to thymectomy versus sham surgery, respectively, followed by total CD4(+) T cell depletion and recovery from this depletion. Although thymectomized and sham-treated RMs manifested comparable CD4(+) T(M) recovery, only sham-treated RMs reconstituted CD4(+) T(N). CD4(+) T(N)-depleted RMs responded to SIVmac239 infection with markedly attenuated SIV-specific CD4(+) T cell responses, delayed SIVenv-specific Ab responses, and reduced SIV-specific CD8(+) T cell responses. However, CD4(+) T(N)-depleted and -repleted groups showed similar levels of SIV replication. Moreover, CD4(+) T(N) deficiency had no significant effect on CD4(+) T(M) homeostasis (either on or off anti-retroviral therapy) or disease progression. These data demonstrate that the CD4(+) T(N) compartment is dispensable for CD4(+) T(M) homeostasis in progressive SIV infection, and they confirm that CD4(+) T(M) comprise a homeostatically independent compartment that is intrinsically capable of self-renewal.
authors.affiliation: Vaccine and Gene Therapy Institute, Department of Pathology, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA.
authors.forename: Afam A
authors.initials: AA
authors.lastname: Okoye
authors.forename: Mukta
authors.initials: M
authors.lastname: Rohankhedkar
authors.forename: Chike
authors.initials: C
authors.lastname: Abana
authors.forename: Audrie
authors.initials: A
authors.lastname: Pattenn
authors.forename: Matthew
authors.initials: M
authors.lastname: Reyes
authors.forename: Christopher
authors.initials: C
authors.lastname: Pexton
authors.forename: Richard
authors.initials: R
authors.lastname: Lum
authors.forename: Andrew
authors.initials: A
authors.lastname: Sylwester
authors.forename: Shannon L
authors.initials: SL
authors.lastname: Planer
authors.forename: Alfred
authors.initials: A
authors.lastname: Legasse
authors.forename: Byung S
authors.initials: BS
authors.lastname: Park
authors.forename: Michael
authors.initials: M
authors.lastname: Piatak
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.forename: Michael K
authors.initials: MK
authors.lastname: Axthelm
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Picker
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018450:Disease Progression; D006706:Homeostasis; D007156:Immunologic Memory; D008253:Macaca mulatta; D008297:Male; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D014779:Virus Replication