Anti-FOXP3 monoclonal antibody, clone 3B22D3

In autoimmunity, the important and fragile balance between immunity and tolerance is disturbed, resulting in abnormal immune responses to the body's own tissues and cells. CD4(+)CD25(hi)FoxP3(+) regulatory T cells (Tregs) induce peripheral tolerance in vivo by means of direct cell-cell contact and release of soluble factors, or indirectly through antigen-presenting cells (APC), thereby controlling auto-reactive effector T cells. Based on these unique capacities of Tregs, preclinical studies delivered proof-of-principle for the clinical use of Tregs for the treatment of autoimmune diseases. To date, the first clinical trials using ex vivo expanded polyclonal Tregs have been completed. These pioneering studies demonstrate the feasibility of generating large numbers of polyclonal Tregs in a good manufacturing practices (GMP)-compliant manner, and that infusion of Tregs is well tolerated by patients with no evidence of general immunosuppression. Nonetheless, only modest clinical results were observed, arguing that a more antigen-specific approach might be needed to foster a durable patient-specific clinical cell therapy without the risk for general immunosuppression. In this review, we discuss current knowledge, applications and future goals of adoptive immune-modulatory Treg therapy for the treatment of autoimmune disease and transplant rejection. We describe the key advances and prospects of the potential use of T cell receptor (TCR)- and chimeric antigen receptor (CAR)-engineered Tregs in future clinical applications. These approaches could deliver the long-awaited breakthrough in stopping undesired autoimmune responses and transplant rejections.

Regulatory T-cells (Tregs) play an important role in cancer immunity but their prognostic impact is controversial in diffuse large B-cell lymphoma (DLBCL). Intratumoral Tregs in DLBCL (n = 70) were evaluated by double-stained CD25 and FOXP3 lymphocytes in formalin-fixed paraffin-embedded tissues, and correlated with clinicopathologic features. We found that increased numbers of intratumoral FOXP3+ lymphocytes (>2.4/HPF) and CD25 + FOXP3+ lymphocytes (>0.8/HPF) are favorable prognosticators (p = .004 andp < .001, respectively) in DLBCL patients, along with age <70 years, stage I-II disease, normal serum LDH level and low IPI scores (p < .001, .002, .002, and <.001, respectively). On multivariate analyses, a higher number of CD25 + FOXP3+ lymphocytes retained prognostic significance (p = .040). Interestingly, higher Treg infiltration correlated with increased infiltration by cytotoxic T-lymphocytes (gamma = 0.294,p = .038) and nodal location (gamma = 0.390,p = .004), but not with infiltration by CD123+ plasmacytoid dendritic cells, which were reported to induce Tregs with immune tolerance. Therefore, congruent with literature meta-analyses, higher intratumoral CD25 + FOXP3+ lymphocytes have a beneficial impact on DLBCL.