Critical role of CD4 T cells in maintaining lymphoid tissue structure for immune cell homeostasis and reconstitution

Ming Zeng, Mirko Paiardini, Jessica C. Engram, Greg J. Beilman, Jeffrey G. Chipman, Timothy W. Schacker, Guido Silvestri, Ashley T. Haase

Research output: Contribution to journalArticle

54 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1856-4867
Number of pages3012
JournalBlood
Volume120
Issue number9
DOIs
StatePublished - Aug 30 2012

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