BALB/c mice have more CD4+CD25+ T regulatory cells and show greater susceptibility to suppression of their CD4+CD25− responder T cells than C57BL/6 mice

Abstract

Increasing evidence indicates that CD4(+)CD25(+) T regulatory (Treg) cells control a wide spectrum of immune responses. The initial identification of CD4(+)CD25(+) Treg cell as a "professional suppressor" was based on observations made in BALB/c mice. This mouse strain is well known to preferentially develop T helper cell type 2 responses, to be more susceptible to intracellular parasite infection, to have a higher tumor incidence, and to be more resistant to the induction of autoimmune diseases, as compared with C57BL/6 (B6) mice. We therefore decided to compare Treg cell function of B6 and BALB/c mice. We observed that the frequency of CD4(+)CD25(+) T cells in the thymus and peripheral lymphoid organs of BALB/c mice was higher than in B6 mice. CD4(+)CD25(+) Treg cells from both mouse strains shared similar phenotypic properties, including expression of characteristic immunological markers and hyporesponsiveness to T cell receptor cross-linking and in their capacity to suppress proliferation of BALB/c CD4(+)CD25(-) T responder (Tres) cells. However, CD4(+)CD25(-) Tres cells from B6 mice were notably less susceptible to suppression by CD4(+)CD25(+) Treg cells from either mouse strain. Our data suggest that the number and the level of suppression of CD4(+)CD25(+) Treg cells for CD4(+)CD25(-) Tres cells may be dictated by genetic background. Our data also suggest that differences in the CD4(+)CD25(+) Treg cell number and the susceptibility of CD4(+)CD25(-) Tres cells may, at least in part, account for the differences in immune response between B6 and BALB/c strains of mice.

Limited Peripheral T Cell Anergy Predisposes to Retinal Autoimmunity

“…Broadly similar findings have also been reported in TCR-insHEL mice (34,36) and therefore it is unlikely that these cells account for the difference in the severity of pancreatic and retinal disease. The relative absence of a significant role for this population in both models may be due to the high affinity of the 3A9 TCR and may also reflect strain differences as endogenous Treg number has been shown to be dependent on background (55,56). Our findings do not exclude an important role for Tregs in retinal tolerance and previous work has demonstrated that the severity of IRBP-induced EAU in WT mice is increased following depletion of CD4 ϩ CD25 ϩ cells (8).…”

The novel CD4+CD25+ regulatory T cell effector molecule fibrinogen-like protein 2 contributes to the outcome of murine fulminant viral hepatitis

“…It has been reported that Tregs overexpress a subset of Th2 response genes including interleukin (IL)-10 and transforming growth factor beta (TGF-␤), 17 suppressing Th1 responses and resulting in Th2 polarization. 18,19 BALB/cJ mice that are known to exhibit a Th2-phenotype 20 have increased numbers of Tregs compared with A/J mice that predominantly mount Th1 immune responses. 21 Others have shown that BALB/cJ mice display nonprotective Th2 responses and these mice are susceptible to infection with other pathogens, including the intracellular parasite Leishmania major, whereas mice that develop a Th1 immune response are protected from infection.…”

Strain-dependent activation of NF-κB in the airway epithelium and its role in allergic airway inflammation

“…In humans, TNF-␣ polymorphisms that lead to elevated TNF-␣ levels have been related to decreased T reg cell numbers (28), and anti-TNF-␣ therapy was shown to increase T reg cell levels in asthma and Crohn's disease (27,39). Contrary to this hypothesis, numbers of T reg cells were decreased in the thymus and lymphoid tissue of C57BL/6 mice compared with BALB/c mice (10). However, the potential differences in the number and function of T reg cells in the lungs of various mouse strains have yet to be clarified.…”