title: Critical role of CD4 T cells in maintaining lymphoid tissue structure for immune cell homeostasis and reconstitution.
abstract: Loss of the fibroblastic reticular cell (FRC) network in lymphoid tissues during HIV-1 infection has been shown to impair the survival of naive T cells and limit immune reconstitution after antiretroviral therapy. What causes this FRC loss is unknown. Because FRC loss correlates with loss of both naive CD4 and CD8 T-cell subsets and decreased lymphotoxin-β, a key factor for maintenance of FRC network, we hypothesized that loss of naive T cells is responsible for loss of the FRC network. To test this hypothesis, we assessed the consequences of antibody-mediated depletion of CD4 and CD8 T cells in rhesus macaques and sooty mangabeys. We found that only CD4 T-cell depletion resulted in FRC loss in both species and that this loss was caused by decreased lymphotoxin-β mainly produced by the CD4 T cells. We further found the same dependence of the FRC network on CD4 T cells in HIV-1-infected patients before and after antiretroviral therapy and in other immunodeficiency conditions, such as CD4 depletion in cancer patients induced by chemotherapy and irradiation. CD4 T cells thus play a central role in the maintenance of lymphoid tissue structure necessary for their own homeostasis and reconstitution.
authors.affiliation: Department of Microbiology, Medical School, University of Minnesota, Minneapolis 55455, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Zeng
authors.forename: Mirko
authors.initials: M
authors.lastname: Paiardini
authors.forename: Jessica C
authors.initials: JC
authors.lastname: Engram
authors.forename: Greg J
authors.initials: GJ
authors.lastname: Beilman
authors.forename: Jeffrey G
authors.initials: JG
authors.lastname: Chipman
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Schacker
authors.forename: Guido
authors.initials: G
authors.lastname: Silvestri
authors.forename: Ashley T
authors.initials: AT
authors.lastname: Haase
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016665:Cercocebus atys; D015658:HIV Infections / Q000276:immunology / Q000378:metabolism; D006706:Homeostasis / Q000276:immunology*; D006801:Humans; D007107:Immune System / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D007150:Immunohistochemistry; D008212:Lymphocyte Depletion; D008221:Lymphoid Tissue / Q000276:immunology* / Q000378:metabolism; D053308:Lymphotoxin-beta / Q000276:immunology / Q000378:metabolism; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000378:metabolism
chemical_list: D053308:Lymphotoxin-beta