Response of Human Oligodendrocytes to Interleukin-2

Author: Otero G.C.   Merrill J.E.  

Publisher: Academic Press

ISSN: 0889-1591

Source: Brain, Behavior, and Immunity, Vol.11, Iss.1, 1997-03, pp. : 24-38

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Abstract

Interleukin 2 (IL-2) directly affects the function of both neurons and glia in the nervous system. It can induce proliferation and differentiation or cause cell death in oligodendrocytes. We have previously cloned the cDNAs for the alpha (alpha), beta (beta), and gamma (gamma) chains of the IL-2 receptor (IL-2R) complex from a human oligodendroglioma cell line TC620. In an effort to characterize the IL-2 receptor (IL-2R) on oligodendrocytes, experiments were performed using recombinant human IL-2 on normal human oligodendrocytes from adult brain tissue and the IL-2-responsive subclone TC620.6A2 of the oligodendroglioma line. The TC620 subclone has the phenotype of an immature oligodendrocyte. At 5 n M IL-2, there was a 2.5-fold increase in proliferation of both normal and malignant human oligodendrocytes. This response was receptor-mediated in that binding of 125 I-IL-2 to TC620.6A2 cells detected a single receptor class for IL-2 with an affinity of 3.6 n M. Immunohistochemical staining of TC620.6A2 cells with a panel of monoclonal antibodies to different epitopes of the human IL-2Ralpha chain demonstrated the presence of IL-2Ralpha on the surface of these cells, in staining patterns which did not always coincide with those found on T cells. Neither the beta nor the gamma chain of the IL-2R complex was detected on human oligodendrocytes by immunohistochemistry. Those antibodies which recognized cell surface IL-2Ralpha epitopes on TC620.6A2 blocked IL-2-induced proliferation, while those which did not detect cell surface IL-2Ralpha epitopes were not inhibitory. This same panel of monoclonal antibodies, when used to probe membrane preparations of TC620.6A2 cells on a Western blot, detected three proteins of 100, 83, and 47 kDa, in contrast to the 55-kDa IL-2Ralpha observed on T cells.