Partial reconstitution of the CD4+-T-cell compartment in CD4 gene knockout mice restores responses to tuberculosis DNA vaccines.

Infection and Immunity
Sushila D'SouzaKris Huygen

Abstract

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+-...Continue Reading

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Citations

Nov 13, 2008·The Journal of Infectious Diseases·Christof GeldmacherMichael Hoelscher
Aug 26, 2014·Expert Opinion on Biological Therapy·Nicolas BruffaertsMarta Romano
Nov 26, 2009·Advanced Drug Delivery Reviews·Sandra ChadwickMansoor Amiji
Dec 10, 2016·Human Vaccines & Immunotherapeutics·Helmy Yusuf, Vicky Kett
Jun 5, 2007·Expert Review of Vaccines·Samuel M BeharYing Wu

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