Cutting Edge: IFN-γ-Producing CD4 T Lymphocytes Mediate Spore-Induced Immunity to Capsulated Bacillus anthracis

Abstract

Virulent strains of Bacillus anthracis produce immunomodulating toxins and an antiphagocytic capsule. The toxin component-protective Ag is a key target of the antianthrax immune response that induces production of toxin-neutralizing Abs. Coimmunization with spores enhances the antitoxin vaccine, and inactivated spores alone confer measurable protection. We aimed to identify the mechanisms of protection induced in inactivated-spore immunized mice that function independently of the toxin/antitoxin vaccine system. This goal was addressed with humoral and CD4 T lymphocyte transfer, in vivo depletion of CD4 T lymphocytes and IFN-γ, and Ab-deficient (μMT−/−) or IFN-γ-insensitive (IFN-γR−/−) mice. We found that humoral immunity did not protect from nontoxinogenic capsulated bacteria, whereas a cellular immune response by IFN-γ-producing CD4 T lymphocytes protected mice. These results are the first evidence of protective cellular immunity against capsulated B. anthracis and suggest that future antianthrax vaccines should strive to augment cellular adaptive immunity.

The Exosporium Layer of Bacterial Spores: a Connection to the Environment and the Infected Host

“…Studies involving passive immunization with spore-specific antisera have produced mixed results. Protection has been reported in some studies but could not be demonstrated in others (148,(157)(158)(159). The distinct difference between the unambiguous benefit obtained with active immunization with PA and spore components and the less clear-cut results obtained via passive immunization involving anti-sporecomponent antibodies underscores the likely involvement of cellular immunity in protection (159).…”

CD4 memory T cells divide poorly in response to antigen because of their cytokine profile

“…Effector cytokine producing CD4 memory T cells have been shown to be protective in viral, bacterial and parasitic infections (36)(37)(38), suggesting that memory CD4 cells may provide protection to the host via an enhanced effector cytokine response that directs other immune cells. Thus, inhibition of proliferation may be a direct and inevitable consequence of the effector functions of the memory cells; somehow during effective immune responses CD4 memory cells must strike the right balance between expansion and effector function.…”

Analysis of a novel spore antigen in Bacillus anthracis that contributes to spore opsonization

“…These findings potentially clarify an ongoing debate about the efficacy of anti-spore antibodies in passive protection studies Enkhtuya et al, 2007). Using their homologous passive protection model, Glomski et al (2007) showed that antispore antibodies are not sufficient to protect mice from an infection. However, Enkhtuya et al (2006), using their heterologous passive protection model, showed that rabbit antibodies can significantly protect mice from an infection when compared to a buffer control.…”

“…It has been demonstrated directly and indirectly by several groups that, in addition to toxin antigens, spore entities also have a protective role in the immune response to an anthrax infection (Brossier et al, 2002;Cohen et al, 2000;Enkhtuya et al, 2006;Glomski et al, 2007;Hahn et al, 2005;Kudva et al, 2005;Welkos et al, 2001).…”