The Human Interleukin-2 Receptor: Analysis of Structure and Function

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71955/1/j.1600-065X.1986.tb01492.x.pd

Expression of interleukin 2 receptors on activated human B cells.

Using anti-Tac, a monoclonal anti-interleukin 2 (IL-2) receptor antibody, we have explored the possibility that certain activated B cells display receptors for IL-2. Resting normal B cells and unselected B cell lines established from normal individuals were Tac antigen negative. In contrast, the cell surface Tac antigen expression was demonstrable on 6 of 10 B cell lines from patients with Burkitt's lymphoma, 5 of 6 B cell lines derived from patients with HTLV-I-associated adult T cell leukemia (including all four that had integrated HTLV-I into their genome), and on certain normal B cells activated with pokeweed mitogen. Furthermore, cloned Epstein-Barr virus-transformed B cell lines derived from Tac-positive normal B cells continued to express the Tac antigen in long-term cultures and manifested high affinity IL-2 receptors identified in binding studies with purified radiolabeled IL-2. The line 5B4 developed in the present study could be induced with purified JURKAT-derived or recombinant IL-2 to express a larger number of IL-2 receptors. Furthermore, the addition of IL-2 to the 5B4 B cell line augmented IgM synthesis, which could be blocked by the addition of anti-Tac. The size of the IL-2 receptors expressed on the cloned normal B cell lines was similar (53,000-57,000 daltons) to that of receptors on phytohemagglutinin-stimulated T cell lymphoblasts. Thus, certain malignant and activated normal B cells display the Tac antigen and manifest high affinity receptors for IL-2. These data suggest that IL-2 may play a role in the differentiation of activated B cells into immunoglobulin-synthesizing and -secreting cells

CD4+ Regulatory and Effector/Memory T Cell Subsets Profile Motor Dysfunction in Parkinson’s Disease

Animal models and clinical studies have linked the innate and adaptive immune system to the pathology of Parkinson’s disease (PD). Despite such progress, the specific immune responses that influence disease progression have eluded investigators. Herein, we assessed relationships between T cell phenotype and function with PD progression. Peripheral blood lymphocytes from two separate cohorts, a discovery cohort and a validation cohort, totaling 113 PD patients and 96 age- and environment-matched caregivers were examined by flow cytometric analysis and T cell proliferation assays. Increased effector/memory T cells (Tem), defined as CD45RO+ and FAS+ CD4+ T cells and decreased CD31+ and α4β7+ CD4+ T cells were associated with progressive Unified Parkinson’s Disease Rating Scale III scores. However, no associations were seen between immune biomarkers and increased age or disease duration. Impaired abilities of regulatory T cells (Treg) from PD patients to suppress effector T cell function was observed. These data support the concept that chronic immune stimulation, notably Tem activation and Treg dysfunction is linked to PD pathobiology and disease severity, but not disease duration. The association of T cell phenotypes with motor symptoms provides fresh avenues for novel biomarkers and therapeutic designs