Monoclonal anti-Lyt-1.1 alloantibody was produced as tissue culture supernatant and administered to mice. The antibody, given intraperitoneally, resulted in the suppression of all T cell functions ...studied, but was without direct effect on B cells. Thus, skin and tumour allograft survival was prolonged and there was suppression of the delayed-type hypersensitivity response; T cell help inthe anti-sheep red blood cell antibody response, responder cells in the mixed lymphocyte reaction (MLR), leucoagglutinin-responsive cells, cytotoxic T cell (Tc) function and the induction of Tc were either totally or partially suppressed, all these responses being mediated by Lyt-1+2- or Lyt-1+2+ cells in CBA/H mice. By contrast, there was no inhibitory effect on the MLR-stimulating or lipopolysaccharide-responsive cells. The administration of the anti-Lyt-1.1 antibody was accompanied by a depletion of Lyt-1.1+ T cells from both spleen and lymph node. These studies indicate that the monoclonal anti-Lyt-1.1 antibody is active in vivo with a selective effect on T cells. The results also have important implications for studies of T cell interactions in the mouse in vivo, and for similar studies in man.
A monoclonal antibody to the Ly-6.2 specificity, defined by strain and tissue distribution, was used to identify the cellular antigens of lymphocytes and tumor cell lines. Sodium dodecyl ...sulfate-polyacrylamide gel electrophoresis analysis of immune precipitates demonstrated that the Ly-6.2 antigen on the surface of thymus and the T lymphoma EL-4 was a protein of 34 kd, whereas spleen cells showed two Ly-6.2 molecules of 34 kd and 56 kd. In vitro translation of EL-4 T-lymphoma poly A+ RNA followed by immunoprecipitation showed the synthesis of two Ly-6.2 precursor polypeptides. These two precursors were translated from separable mRNA molecules; the larger encoded a 54 kd polypeptide, while the second, smaller one translated a 36 kd polypeptide. Thus, the T lymphoma EL-4 contains two distinct mRNA, but only one is seen on the surface, while spleen cells contain and translate both mRNAs and both surface forms are detected. What determines the utilization of the two mRNAs and the surface expression of the two different proteins in the different tissues is not known. Whether the two mRNAs are the transcripts of one gene or arise by transcription of two separate but closely linked genes remains to be determined.
The major human Fc receptor, FcgammaRIIa, is the most widespread activating FcR. Our aim was to determine the role of FcgammaRIIa in a transgenic mouse model of immune complex-mediated autoimmunity ...and to characterize the development of spontaneous autoimmune disease.
Arthritis was induced in normal and FcgammaRIIa-transgenic mice by immunization with type II collagen (CII) or by transfer of arthritogenic anti-CII antibodies. Also, mice that spontaneously developed autoimmune disease were assessed by clinical scoring of affected limbs, histology and serology, and measurement of autoantibody titers and cytokine production.
FcgammaRIIa-transgenic mice developed collagen-induced arthritis (CIA) more rapidly than did archetypal CIA-sensitive DBA/1 (H-2q) mice, while nontransgenic C57BL/6 (H-2b) mice did not develop CIA when similarly immunized. Passive transfer of a single dose of anti-CII antibody induced a more rapid, severe arthritis in FcgammaRIIa-transgenic mice than in nontransgenic animals. In addition, most immune complex-induced production of tumor necrosis factor alpha by activated macrophages occurred via FcgammaRIIa, not the endogenous mouse FcR. A spontaneous, multisystem autoimmune disease developed in aging (>20 weeks) transgenic mice (n = 25), with a 32% incidence of arthritis, and by 45 weeks, all mice had developed glomerulonephritis and pneumonitis, and most had antihistone antibodies. Elevated IgG2a levels were seen in mice with CIA and in those with spontaneous disease.
The presence of enhanced passive and induced autoimmunity, as well as the emergence of spontaneous autoimmune disease at 20-45 weeks of age, suggest that FcgammaRIIa is a very important factor in the pathogenesis of autoimmune inflammation and a possible target for therapeutic intervention.
The fluorescence-activated cell sorter (FACS) was used to examine the expression of several alloantigens on T cells: Thy-1, Lyt-1.1, Lyt-2.1, Ly-5, Ly-6 and Ly-7. Antibodies secreted by monoclonal ...cell lines were used to characterize the Thy-1:2, Lyt-1.1 and Lyt-2.1 antigenic determinants, whereas Ly-5.1, Ly-6.2 and Ly-7.2 determinants were identified with alloantisera raised by conventional hyperimmunization. Using indirect immunofluorescence with fluorescein isothiocyanate-conjugated reagents, the profiles obtained with the FACS demonstrated that: (a) the expression of Thy-1 is greater on normal thymocytes than on cortisone-resistant thymocytes (CRT), lymph node and spleen cells; (b) in contrast to Thy-1, the expression of Ly-1 on normal thymocytes is less than on CRT, lymph node and spleen cells; (c) about 90% of normal thymocytes abut less than 50% of CRT, spleen and lympho node T cells are Lyt-2+ and (d) although weakly expressed on normal thymocytes, the amount of Ly-6 and Ly-7 present on peripheral T cells was considerably increased. The significance of these findings and the potential for further analysis of T cell developmental pathways is discussed.
There is no denying that race is a critical issue in understanding the South. However, this concluding volume of The New Encyclopedia of Southern Culture challenges previous understandings, revealing ...the region's rich, ever-expanding diversity and providing new explorations of race relations. In 36 thematic and 29 topical essays, contributors examine such subjects as the Tuskegee Syphilis Study, Japanese American incarceration in the South, relations between African Americans and Native Americans, Chinese men adopting Mexican identities, Latino religious practices, and Vietnamese life in the region. Together the essays paint a nuanced portrait of how concepts of race in the South have influenced its history, art, politics, and culture beyond the familiar binary of black and white.
Objective
To identify intervals containing systemic lupus erythematosus (SLE) susceptibility alleles in the BXSB strain of mice.
Methods
We analyzed 286 (B10 × B10 × BXSBF1) backcross mice for a ...range of phenotypic traits associated with the development of SLE in BXSB mice. The mice were genotyped using 93 microsatellite markers, and the linkage of these markers to disease was studied by extreme‐phenotype and quantitative trait locus analysis.
Results
The disease phenotype in these backcross mice was less severe than that in BXSB mice. However, antinuclear antibody production was increased compared with the parental strain. We identified 4 areas of genetic linkage to disease on chromosome 1 (Bxs1–4), 1 on chromosome 3 (Bxs5), and another interval on chromosome 13 which were associated with various aspects of the phenotype. Bxs4 and Bxs5 are located in regions not previously linked to disease in other models of SLE.
Conclusion
SLE in the BXSB mouse model has a complex genetic basis and involves at least 5 distinct intervals located on chromosomes 1 and 3. There is evidence that different intervals affect particular aspects of the SLE phenotype.
