Treatment with interleukin-7 restores host defense against Pneumocystis in CD4+ T-lymphocytedepleted mice

S. Ruan, D. R. Samuelson, B. Assouline, M. Morre, J. E. Shellito

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Pneumocystis pneumonia (PCP) is a major cause of morbidity and mortality in patients with HIV infection. CD4+ T lymphocytes are critical for host defense against this infection, but in the absence of CD4+ T lymphocytes, CD8+ T lymphocytes may provide limited host defense. The cytokine interleukin-7 (IL-7) functions to enhance lymphocyte proliferation, survival, and recruitment of immune cells to sites of infection. However, there is little known about the role of IL-7 in PCP or its potential use as an immunotherapeutic agent. We hypothesized that treatment with recombinant human IL-7 (rhIL-7) would augment host defense against Pneumocystis and accelerate pathogen clearance in CD4-depleted mice. Control and CD4-depleted mice were infected with Pneumocystis, and rhIL-7 was administered via intraperitoneal injection. Our studies indicate that endogenous murine IL-7 is part of the normal host response to Pneumocystis murina and that administration of rhIL-7 markedly enhanced clearance of Pneumocystis in CD4-depleted mice. Additionally, we observed increased recruitment of CD8+ T lymphocytes to the lungs and decreased apoptosis of pulmonary CD8+ T lymphocytes in rhIL-7-treated animals compared to those in untreated mice. The antiapoptotic effect of rhIL-7 was associated with increased levels of Bcl-2 protein in T lymphocytes. rhIL-7 immunotherapy in CD4-depleted mice also increased the number of gamma interferon (IFN-γ)-positive CD8+ central memory T lymphocytes in the lungs. We conclude that rhIL-7 has a potent therapeutic effect in the treatment of murine Pneumocystis pneumonia in CD4-depleted mice. This therapeutic effect is mediated through enhanced recruitment of CD8+ T cells and decreased apoptosis of lung T lymphocytes, with a preferential action on central memory CD8+ T lymphocytes.

Original languageEnglish (US)
Pages (from-to)108-119
Number of pages12
JournalInfection and immunity
Volume84
Issue number1
DOIs
StatePublished - Jan 1 2015

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Pneumocystis
Interleukin-7
T-Lymphocytes
Pneumocystis Pneumonia
Therapeutics
Lung
Therapeutic Uses
Apoptosis
Murinae
Infection
Intraperitoneal Injections
Immunotherapy
Interferon-gamma
HIV Infections

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Treatment with interleukin-7 restores host defense against Pneumocystis in CD4+ T-lymphocytedepleted mice. / Ruan, S.; Samuelson, D. R.; Assouline, B.; Morre, M.; Shellito, J. E.

In: Infection and immunity, Vol. 84, No. 1, 01.01.2015, p. 108-119.

Research output: Contribution to journalArticle

Ruan, S. ; Samuelson, D. R. ; Assouline, B. ; Morre, M. ; Shellito, J. E. / Treatment with interleukin-7 restores host defense against Pneumocystis in CD4+ T-lymphocytedepleted mice. In: Infection and immunity. 2015 ; Vol. 84, No. 1. pp. 108-119.
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