In this three-month trial TNFR:Fc was safe, well tolerated, and associated with improvement in the inflammatory symptoms of rheumatoid arthritis.

Interleukin-1 alpha and -1 beta (IL-1 alpha and IL-1 beta) are cytokines that participate in the regulation of immune responses, inflammatory reactions, and hematopoiesis. A direct expression strategy was used to clone the receptor for IL-1 from mouse T cells. The product of the cloned complementary DNA binds both IL-1 alpha and IL-1 beta in a manner indistinguishable from that of the native T cell IL-1 receptor. The extracellular, IL-1 binding portion of the receptor is 319 amino acids in length and is composed of three immunoglobulin-like domains. The cytoplasmic portion of the receptor is 217 amino acids long.

No abstract

IL-4, a pleiotropic cytokine produced by T lymphocytes, plays an important role in immune responsiveness by regulating proliferation and differentiation of a variety of lymphoid and myeloid cells via binding to high affinity receptors. In this report we describe the isolation and functional expression of a human IL-4-R cDNA. When transfected into COS-7 cells, the cDNA encodes a 140-kD cell-surface protein. After transfection into a murine T cell line, the cDNA encodes a protein that binds human IL-4 with high affinity and can confer responsiveness to human IL-4. The predicted extracellular domain of the IL-4-R exhibits significant amino acid sequence homology with the beta subunit of the IL-2-R (p75), and the receptors for IL-6, erythropoietin, and prolactin. These receptors comprise a novel superfamily with extracellular domains characterized by four conserved cysteine residues and a double tryptophan-serine (WSXWS) motif located proximal to the transmembrane region.

The mixed leukocyte culture (MLC) t test has been used as a measure of histocompatibility and as a model of the recognition phase of the homograft reaction. Studies in man (I), mouse (2), and rat (3) have suggested that activation or stimulation in MLC is dependent on differences at the major histocompatibility complex (MHC) although exceptions to this rule have been found (4). In the mouse the MHC includes two serologically defined (SD) loci, H-2K and H-2D, immune response (Ir) loci (5, 6), loci governing susceptibility or resistance to tumor viruses (7), and the Ss-Slp loci (8).It was naturally assumed that since MLC activation was dependent on MHC differences, SD antigen differences were responsible for stimulation. Unusual and aberrant cases in human studies (9-12) suggested, however, that in addition to the SD loci, there may be MHC differences which are difficult to detect serologically using the usual methods of immunization and testing, but which can cause a lymphocyte proliferative response. We will refer to such differences as lymphocyte-defined (LD) differences (13).We will present data in this paper which we have obtained in mouse MLC studies. We have for the most part made use of congenic strains of animals carrying recombinant M H C chromosomes (strains that are genetically identical except for the genes of the MHC). This allows us to test two animals differing for only some segment of the MHC. In a few cases we have studied animals differing for the M H C and for loci segregating independently of the M H C ; these will be discussed in detail. Our results indicate that the strongest MLC activation is associated with Ir