Roles of CD4⁺T Cells and Gamma Interferon in Protective Immunity againstBabesia microtiInfection in Mice

Abstract

Babesia microti produces a self-limiting infection in mice, and recovered mice are resistant to reinfection. In the present study, the role of T cells in protective immunity against challenge infection was examined. BALB/c mice which recovered from primary infection showed strong protective immunity against challenge infection. In contrast, nude mice which failed to control the primary infection and were cured with an antibabesial drug did not show protection against challenge infection. Treatment of immune mice with anti-CD4 monoclonal antibody (MAb) diminished the protective immunity against challenge infection, but treatment with anti-CD8 MAb had no effect on the protection. Transfer of CD4+ T-cell-depleted spleen cells resulted in higher parasitemia than transfer of CD8+ T-cell-depleted spleen cells. A high level of gamma interferon (IFN-γ), which was produced by CD4+ T cells, was observed for the culture supernatant of spleen cells from immune mice, and treatment of immune mice with anti-IFN-γ MAb partially reduced the protection. Moreover, no protection against challenge infection was found in IFN-γ-deficient mice. On the other hand, treatment of immune mice with MAbs against interleukin-2 (IL-2), IL-4, or tumor necrosis factor alpha did not affect protective immunity. These results suggest essential requirements for CD4+ T cells and IFN-γ in protective immunity against challenge infection with B. microti.

Increased Arthritis Severity in Mice Coinfected withBorrelia burgdorferiandBabesia microti

“…Th1 cytokine responses are thought to dominate in B. microti infections-at least during acute infection [12]. IFN-g has been reported to have some role in the resolution of acute infection of mice infected with B. microti and to be involved in protection against other intracellular parasites.…”

Human Babesiosis

“…In addition, patients who suffer from lymphoproliferative disorders of the B cell compartment and are treated with regimens that deplete B cells also are at risk for persistent or relapsing babesiosis, [55] suggesting an important role for B cells in host resistance. However, studies of B. microti infection in mice do not provide strong evidence of a role for B cells and immunoglobulins in host resistance, [82,[95][96][97] implying that additional immune dysfunction is required for symptomatic babesiosis to develop in patients with B cell proliferative disorders.…”

Prospects for recombinant vaccines against Babesia bovis and related parasites

“…The requirement for IFN-γ is less clear. One study using IFN-γ knockout mice showed delayed but eventual resolution of disease caused by B. microti (21), whereas a separate study showed no protection against challenge with this parasite in mice depleted of IFN-γ by specific antibody treatment (20). Differences may be related to the use of different parasite strains.…”