Although the beneficial effects of probiotics on wide variety of diseases have been shown, little is known about how probiotics modulate the immune system. In this study we elucidated the underlying mechanisms how Lactobacillus casei (L. casei) protects against rheumatoid arthritis (RA) progression by investigating the effector functions of CD4(+) T cells. Oral administration of L. casei suppressed collagen-induced arthritis (CIA) and reduced paw swelling, lymphocyte infiltration and destruction of cartilage tissue. L. casei administration reduced type II collagen (CII)-reactive proinflammatory molecules (IL-1beta, IL-2, IL-6, IL-12, IL-17, IFN-gamma, TNF-alpha and Cox-2) by CD4(+) T cells. L. casei administration also reduced translocation of NF-kappaB into nucleus and CII-reactive Th1-type IgG isotypes IgG2a and IgG2b, while up-regulating immunoregulatory IL-10 levels. Our results suggest that oral administration of L. casei suppresses the type II collagen-reactive effector function of Th1-type cellular and humoral immune responses in arthritic inflammation.