IL-15 induces CD4+ effector memory T cell production and tissue emigration in nonhuman primates

Louis Picker, Edward F. Reed-Inderbitzin, Shoko I. Hagen, John B. Edgar, Scott Hansen, Alfred Legasse, Shannon Planer, Michael Piatak, Jeffrey D. Lifson, Vernon C. Maino, Michael Axthelm, Francois Villinger

Research output: Contribution to journalArticle

135 Citations (Scopus)

Abstract

HIV infection selectively targets CD4+ effector memory T (T EM) cells, resulting in dramatic depletion of CD4+ T cells in mucosal effector sites in early infection. Regeneration of the T EM cell compartment is slow and incomplete, even when viral replication is controlled by antiretroviral therapy (ART). Here, we demonstrate that IL-15 dramatically increases in vivo proliferation of rhesus macaque (RM) CD4+ and CD8+ TEM cells with little effect on the naive or central memory T (TCM) cell subsets, a response pattern that is quite distinct from that of either IL-2 or IL-7. TEM cells produced in response to IL-15 did not accumulate in blood. Rather, 5-bromo-2′-deoxyuridine (BrdU) labeling studies suggest that many of these cells rapidly disperse to extralymphoid effector sites, where they manifest (slow) decay kinetics indistinguishable from that of untreated controls. In RMs with uncontrolled SIV infection and highly activated immune systems, IL-15 did not significantly increase CD4+ TEM cell proliferation, but with virologic control and concomitant reduction in immune activation by ART, IL-15 responsiveness was again observed. These data suggest that therapeutic use of IL-15 in the setting of ART might facilitate specific restoration of the CD4+ T cell compartment that is the primary target of HIV with less risk of exhausting precursor T cell compartments or generating potentially deleterious regulatory subsets.

Original languageEnglish (US)
Pages (from-to)1514-1524
Number of pages11
JournalJournal of Clinical Investigation
Volume116
Issue number6
DOIs
StatePublished - Jun 1 2006

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Interleukin-15
Emigration and Immigration
Primates
T-Lymphocytes
T-Lymphoid Precursor Cells
Interleukin-7
T-Lymphocyte Subsets
Therapeutic Uses
Bromodeoxyuridine
Infection
Macaca mulatta
HIV Infections
Interleukin-2
Regeneration
Immune System
Therapeutics
Cell Proliferation
HIV

ASJC Scopus subject areas

  • Medicine(all)

Cite this

IL-15 induces CD4+ effector memory T cell production and tissue emigration in nonhuman primates. / Picker, Louis; Reed-Inderbitzin, Edward F.; Hagen, Shoko I.; Edgar, John B.; Hansen, Scott; Legasse, Alfred; Planer, Shannon; Piatak, Michael; Lifson, Jeffrey D.; Maino, Vernon C.; Axthelm, Michael; Villinger, Francois.

In: Journal of Clinical Investigation, Vol. 116, No. 6, 01.06.2006, p. 1514-1524.

Research output: Contribution to journalArticle

Picker, L, Reed-Inderbitzin, EF, Hagen, SI, Edgar, JB, Hansen, S, Legasse, A, Planer, S, Piatak, M, Lifson, JD, Maino, VC, Axthelm, M & Villinger, F 2006, 'IL-15 induces CD4+ effector memory T cell production and tissue emigration in nonhuman primates', Journal of Clinical Investigation, vol. 116, no. 6, pp. 1514-1524. https://doi.org/10.1172/JCI27564
Picker, Louis ; Reed-Inderbitzin, Edward F. ; Hagen, Shoko I. ; Edgar, John B. ; Hansen, Scott ; Legasse, Alfred ; Planer, Shannon ; Piatak, Michael ; Lifson, Jeffrey D. ; Maino, Vernon C. ; Axthelm, Michael ; Villinger, Francois. / IL-15 induces CD4+ effector memory T cell production and tissue emigration in nonhuman primates. In: Journal of Clinical Investigation. 2006 ; Vol. 116, No. 6. pp. 1514-1524.
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