CD4+ T Cell-Independent Vaccination Against Pneumocystis Carinii in Mice

J Clin Invest. 2001 Nov;108(10):1469-74. doi: 10.1172/JCI13826.

Abstract

Host defenses are profoundly compromised in HIV-infected hosts due to progressive depletion of CD4+ T lymphocytes. Moreover, deficient CD4+ T lymphocytes impair vaccination approaches to prevent opportunistic infection. Therefore, we investigated a CD4+ T cell-independent vaccine approach to a prototypic AIDS-defining infection, Pneumocystis carinii (PC) pneumonia. Here, we demonstrate that bone marrow-derived dendritic cells (DCs) expressing the murine CD40 ligand, when pulsed ex vivo by PC antigen, elicited significant titers of anti-PC IgG in CD4-deficient mice. Vaccinated animals demonstrated significant protection from PC infection, and this protection was the result of an effective humoral response, since adoptive transfer of CD4-depleted splenocytes or serum conferred this protection to CD4-deficient mice. Western blot analysis of PC antigen revealed that DC-vaccinated, CD4-deficient mice predominantly reacted to a 55-kDa PC antigen. These studies show promise for advances in CD4-independent vaccination against HIV-related pathogens.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adoptive Transfer
  • Animals
  • Base Sequence
  • CD4-Positive T-Lymphocytes / immunology*
  • DNA Primers
  • Fungal Vaccines / administration & dosage*
  • Lymphocyte Activation
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Pneumocystis / immunology*
  • Pneumonia, Pneumocystis / prevention & control*

Substances

  • DNA Primers
  • Fungal Vaccines