CD4+ T cell-independent vaccination against Pneumocystis carinii in mice.
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.
Zheng
M
M
Section of Pulmonary and Critical Care, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA.
Shellito
J E
JE
Marrero
L
L
Zhong
Q
Q
Julian
S
S
Ye
P
P
Wallace
V
V
Schwarzenberger
P
P
Kolls
J K
JK
D019264:Adoptive Transfer; D000818:Animals; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D017931:DNA Primers; D005657:Fungal Vaccines / Q000008:administration & dosage*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011010:Pneumocystis / Q000276:immunology*; D011020:Pneumonia, Pneumocystis / Q000517:prevention & control*
D017931:DNA Primers; D005657:Fungal Vaccines