CD8 Knockout Mice Are Protected from Challenge by Vaccination with WR201, a Live Attenuated Mutant ofBrucella melitensis

Abstract

CD8+ T cells have been reported to play an important role in defense against B. abortus infection in mouse models. In the present report, we use CD8 knockout mice to further elucidate the role of these cells in protection from B. melitensis infection. Mice were immunized orally by administration of B. melitensis WR201, a purine auxotrophic attenuated vaccine strain, then challenged intranasally with B. melitensis 16M. In some experiments, persistence of WR201 in the spleens of CD8 knockout mice was slightly longer than that in the spleens of normal mice. However, development of anti-LPS serum antibody, antigen-induced production of γ-interferon (IFN-γ) by immune splenic lymphocytes, protection against intranasal challenge, and recovery of nonimmunized animals from intranasal challenge were similar between normal and knockout animals. Further, primary Brucella infection was not exacerbated in perforin knockout and Fas-deficient mice and these animals' anti-Brucella immune responses were indistinguishable from those of normal mice. These results indicate that CD8+ T cells do not play an essential role as either cytotoxic cells or IFN-γ producers, yet they do participate in a specific immune response to immunization and challenge in this murine model of B. melitensis infection.

Targeting resident memory T cell immunity culminates in pulmonary and systemic protection against Brucella infection

“…CD8 + T cells were assumed to be less important for protection against brucellosis than CD4 + T cells, and CD8 + T cell immunity was thought to be limited to cytotoxicity [11,15,20,72,73]. In fact, CD8 -/mice orally vaccinated with the attenuated B. melitensis WR201 strain showed no loss of protection against pulmonary challenge with virulent wt B. melitensis demonstrating that CD8 + T cells are not crucial for protection from pulmonary Brucella infection [74]. To interrogate the relevance of the induced T cell subsets, various studies were undertaken to define the mechanism of protection.…”

Nasal vaccination stimulates CD8+ T cells for potent protection against mucosal Brucella melitensis challenge

“…Orally administered live, attenuated B. melitensis WR201 vaccine showed that CD8 + T cells were dispensable since vaccinated CD8 −/− mice remained protected against nasal B. melitensis challenge. 25 For M. tb , it has been shown that routes of immunization can influence the adaptive immune responses against pulmonary challenge. Nasal vaccination with a recombinant adenovirus vaccine expressing M. tb Ag85A was able to effectively activate both CD4 + and CD8 + T cells in the lungs, particularly within the airway lumen.…”

“…12,18,19 However, how the relative contributions by CD4 + and CD8 + T cells aid to protect against Brucella infections are less well understood. Several studies [20][21][22] have suggested that CD4 + and CD8 + T cells are both necessary in protection against brucellosis, whereas others advocated the importance of CD4 + T cells [23][24][25][26] or CD8 + T cells. 15,[27][28][29] Such T-cell biases may arise from attributes of the vaccine used or modes of delivery.…”

Vaccination with a ΔnorD ΔznuA Brucella abortus mutant confers potent protection against virulent challenge

“…Although the numbers of cytokine-producing CD4 + T cells exceeded CD8 + T cells in znBAZ-vaccinated mice, about one-third of the total IFN-γproducing TCRβ + cells were CD8 + T cells. It has been presumed that CD4 + T cells are the major source for IFN-γ and TNF-α [42,43], and only a handful of studies has implicated the importance of CD8 + T cells [40,44]. The route of vaccination may be a contributing factor in CD8 T cell elevations [19, 45, 46].…”