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.

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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

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Transgenic mice lacking an intact P2-microglobulin (J32m) gene fail to express major histocompatibility complex (MHC) class I proteins on the cell surface and, as a result, are virtually devoid of CD4-CD8+ lymphocytes. These animals provide a unique model system for directly assessing the role of CD8+ lymphocytes in the modulation of viral infection in vivo. P2m_ CD8-mice and their normal littermates were inoculated at the base of the tail with the WR strain of vaccinia virus and monitored for serum antibody and lesion formation. Both groups developed similar lesions in response to a broad virus dose range, and all animals had completely recovered by day 28 after inoculation. Isotypespecifi immunogibulin levels were determined for each animal on day 7 and day 14 after primary inoculation, and again 7 days after a virus challenge. The virus-specific IgG1, IgG2a, and IgG2b levels were signifcantly different in the (2m-/-group (20-, 9-, and 30-fold lower, respectively, on day 7 after challenge) compared with the f2m+ /-group. Virus-specific serum IgM levels for both groups remained similar throughout the experiment. In a separate experiment, 32m-/-mice were immunized with a nonviral antigen, 2,4,6-trinitrophenylconjugated keyhole limpet hemocyanin, and both total and antigen-specific isotype-specific immunoglobulin titers were determined. Total IgG1, IgG2a, IgG2b, and IgG3 tended to be iower overall in the f2m-/-mice compared with j82m+/-littermates. In contrast, total and antigen-specific IgE titers were similar in the two groups. These data indicate that CD81 lymphocytes are not required to clear high doses of vaccinia virs, and they suggest that f21m/-mice are less efficient at antigen-specific IgG production than their (3m+/-littermates.

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