TY - JOUR T1 - Partial reconstitution of the CD4+-T-cell compartment in CD4 gene knockout mice restores responses to tuberculosis DNA vaccines. JF - Infect Immun Y1 - 2006 A1 - D'Souza, Sushila A1 - Marta Romano A1 - Korf, Johanna A1 - Wang, Xiao-Ming A1 - Adnet, Pierre-Yves A1 - Huygen, Kris KW - Acyltransferases KW - Animals KW - Antibodies, Bacterial KW - Antigens, Bacterial KW - Antigens, CD4 KW - Bacterial Proteins KW - CD4-Positive T-Lymphocytes KW - Cytokines KW - Female KW - Interferon-gamma KW - Lung KW - mice KW - Mice, Inbred C57BL KW - Mice, Knockout KW - T-Lymphocytes, Cytotoxic KW - Tuberculosis Vaccines KW - Vaccination KW - Vaccines, DNA AB -

Reactivation tuberculosis (TB) is a serious problem in immunocompromised individuals, especially those with human immunodeficiency virus (HIV) coinfection. The adaptive immune response mediated by CD4+ and CD8+ T cells is known to confer protection against TB. Hence, vaccines against TB are designed to activate these two components of the immune system. Anti-TB DNA vaccines encoding the immunodominant proteins Ag85A, Ag85B, and PstS-3 from Mycobacterium tuberculosis are ineffective in mice lacking CD4+ T cells (CD4-/- mice). In this study, we demonstrate that reconstitution of the T-cell compartment in CD4-/- mice restores vaccine-specific antibody and gamma interferon (IFN-gamma) responses to these DNA vaccines. The magnitude of the immune responses correlated with the extent of reconstitution of the CD4+-T-cell compartment. Reconstituted mice vaccinated with DNA encoding PstS-3, known to encode a dominant D(b)-restricted CD8+-T-cell epitope, displayed CD8+-T-cell responses not observed in CD4-/- mice. M. tuberculosis challenge in reconstituted mice led to the extravasation of IFN-gamma-producing CD4+ and CD8+ T cells into lungs, the primary site of bacterial replication. Importantly, a reconstitution of 12 to 15% of the CD4+-T-cell compartment resulted in Ag85B plasmid DNA-mediated protection against a challenge M. tuberculosis infection. Our findings provide evidence that anti-TB DNA vaccines could be effective in immunodeficient individuals after CD4+-T-lymphocyte reconstitution, as may occur following antiretroviral therapy in HIV+ patients.

VL - 74 CP - 5 U1 - http://www.ncbi.nlm.nih.gov/pubmed/16622212?dopt=Abstract M3 - 10.1128/IAI.74.5.2751-2759.2006 ER -