Cytokines and Lymphocyte Activation

It is well known that the activation of lymphoid cells differ significantly depending on their lineage/subset and differentiation stages. Among the variety of cytokines characterized until today, essentially all the cytokines appear not to be strictly specific to any of the subset of lymphocytes. For example, all the interleukins including IL-2, IL-4 and IL-5 are not specific for B or T lymphocytes. The multiple target specificity is a general property of interleukins and cytokines. The most typical examples may be IL-1 and IL-6 having a very broad target specificity. Many interleukins show B cell activation or differentiating activities, besides the activities on T cells. IL-1, IL-2, IL-4, IL-5 and IL-6 are the examples. Among these, IL-2 and IL-4 are known to act on the immature B cells, while IL-5 and IL-6 seem to activate the mature B cells. We have comparatively studied IL-4 and IL-2 systems, because of their principal involvement in the B and T cell activation, respectively. IL-4 is known to augment the immunoglobulin production particularly of IgE class. At the same time, IL-4 induces the expression of low affinity Fc receptor for IgE (FcƒÃR•a). This FcƒÃR•a is deeply involved in the physiological and pathological B cell activation in human. 1) Because of the affinity to IgE, this receptor and the soluble receptor (IgE binding factor) is considered to play various important regulatory roles in IgE metabolism . FcƒÃR•a gene expression is mainly induced on B cells and monocyte/macrophages by apropriate inducing stimuli. In activated or pathological condition , T cells and eosinophils also express FcƒÃR•a. While IL-4 is a general inducer of FcƒÃR•a on all these cell types, ƒÁIFN counteracts the IL-4 action to induce FcƒÃR•a and IgE production by B cells. However, ƒÁIFN enhaces the expression of FcƒÃR•a on non-B cells including monocyte/macrophages and eosinophiles, based on the study using cell lines. 2) FcƒÃR•a is identical to the B cell activation actigen CD23, which is known to be strongly expressed on B lymphoblastoid cell lines transormed by Ebstein-Barr virus