Profound CD4+/CCR5+ T cell expansion is induced by CD8+ lymphocyte depletion but does not account for accelerated SIV pathogenesis

Afam Okoye, Haesun Park, Mukta Rohankhedkar, Lia Coyne-Johnson, Richard Lum, Joshua M. Walker, Shannon L. Planer, Alfred W. Legasse, Andrew W. Sylwester, Michael Piatak, Jeffrey D. Lifson, Donald L. Sodora, Francois Villinger, Michael K. Axthelm, Joern E. Schmitz, Louis J. Picker

Research output: Contribution to journalArticle

56 Scopus citations

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+ TEM 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+ TEM and TTrM 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.

Original languageEnglish (US)
Pages (from-to)1575-1588
Number of pages14
JournalJournal of Experimental Medicine
Volume206
Issue number7
DOIs
StatePublished - Jul 6 2009

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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