Milgrom symposium.
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Allergy and Immunology↗
Biomedical subjects
S Dubiski
Publications and source records attributed to S Dubiski.
Retrovirus-induced lymphoproliferative disease in mice: role of humoral immunity in perinatally exposed mice.
The mice born to female mice infected with LP-BM5 MuLV, the etiologic agent for lymphoproliferative disease and nursed for 4-6 weeks by them were less susceptible upon reinfection by i.v. transfusion of blood or plasma from infected donors with fully developed disease. Sera of 7 week or older perinatally exposed mice were capable of a complete in vitro neutralization of virus in plasma or blood from mice with fully developed disease. In contrast, sera from 3-week old perinatally exposed mice were ineffective. The neutralizing ability of the sera was drastically reduced or abrogated after their absorption with anti-mouse IgM. These observations are consistent with the notion that perinatally exposure results ina moderate form of the disease of the offspring. This perinatal infection is followed by a production of neutralizing antibodies of predominantly the IgM class that significantly alters the course of the lymphoproliferative disease and, in some instances, even prevents its development.
Animals↗
Age-related changes in interleukin production in BALB/cNNia and SJL/J mice and their modification after administration of foreign macromolecules.
In vitro production of Interleukin-2, -3, -4 and -10 by activated lymphocytes of BALB/cNNia and SJL/J was studied. While IL-2 production in BALB/c mice remains constant throughout the life span of the animals (8-113 weeks), an increase in production from stimulated SJL cells was seen. Age-related increases in IL-3 and IL-4 production occur between young and middle age (8-60 weeks) in both strains. Some organ differences in quantity of lymphokine produced were seen; the direction of age-related changes was the same for lymphocytes of spleen and MLN. The exceptional feature of BALB/cNNia was the relative stabilization of the levels of interleukin production, as animals approach old age. BALB/cNNia and SJL, which are at the two opposite extremes of lifespan, differ also in their response to molecular interventions: in BALB/cNNia fetal sheep liver extract and hemocyanin increase the output of interleukins. This is in striking contrast to the effects observed in older SJL mice in which the extract reduced the output of IL-3 and IL-4 by old animals, whereas hemocyanin increased the output of IL-2 and IL-3 at all ages tested.
Aging↗
Age-related polymorphism of thymus subpopulations in inbred mice.
There are striking age-related changes in the demography of thymus lymphocytes, i.e. in thymus-cell subpopulations of BALB/c and SJL mice; these changes occur in the proportion of cells, identified by various markers, and by the membrane density of these markers. The thymuses of both strains undergo an age-related increase in the proportion of CD4+ CD8- cells and decrease in CD4+ CD8+ cells. Age-related changes in cells that are Pgp-1+ also show marked strain differences: Pgp-1+ cells increase in SJL, but not in BALB/c thymuses. In both strains, cells with high density of Pgp-1 appear in later life, though this is more marked in the thymus of SJL, which also shows a higher relative density at an advanced age, than do BALB/c mice. Furthermore, the per cent of cells with high density of Pgp-1 is larger in thymuses of SJL than in BALB/c mice. The percentage of CD45+ thymocytes remains unchanged, as animals age. Thymocyte-membrane densities of CD-45 undergo age-related increases in both SJL and BALB/c. The per cent of cells with high density of CD-45 is similar in both strains. Individual variations in relative size of subpopulations in SJL mice of the same age are greater in old than in young mice; this increase in heterogeneity is manifested by increase in standard deviation. Corresponding significant changes have not been observed in BALB/c or C57BL/6 mice. Thus, we have detected an intrastrain variation which may reflect age-related effects of the impact of stochastic events.
Aging↗
Glomerular lesions induced in the rabbit by physicochemically altered homologous IgG.
Immunization of rabbits with physicochemically altered homologous or even autologous IgG induces formation of antibodies combining with IgG of rabbit and of foreign species. Cardiac but not renal lesions were reported in such animals. This study examined the nephritogenic potential of the immune response to cationized or heat-aggregated homologous IgG of b9 or b4 allotype in rabbits of the b4 allotype. Rabbits injected with either b9 or b4 cationized IgG produced antibodies reactive with rabbit and human IgG and with histones; they also developed abnormal glomerular deposits of IgG b4 and C3 corresponding to alterations of the glomerular basement membranes (GBM). Rabbits injected with either b9 or b4 aggregated IgG developed antibodies reactive with rabbit and human IgG and abnormal glomerular deposits of IgG b4 and C3 in the GBM and in the mesangium with subendothelial and mesangial electron-dense deposits. Some rabbits in both groups had proliferative and exudative glomerulonephritis and proteinuria. The results showed that immunization of rabbits with physicochemically altered homologous IgG induces an immune response to rabbit and human IgG and to histones as well as glomerular deposits of autologous IgG and C3 and other glomerular lesions.
Animals↗
Economic correction; quantity and age-related rate of change.
Correlation between the relative magnitude of activity or concentration in youth and the relative magnitude of age-related decrease occurs in several systems. We have observed this correlation in density of D2-dopamine receptors of the striatal membrane, activity of lymphocyte activated killer cells, relative density of CD8 on thymocytes, augmenting activity of T splenocytes and mRNA, coding for IL-1 in Langerhans cells. We have suggested that this correlation should be considered in the context of balanced investment in lifespan and reproductive efficiency, that it may be the result of feedback regulation and have designated it as "economic correction".
Age Factors↗
Strain polymorphism in progression of aging: changes in CD4, CD8 bearing subpopulations.
Polymorphism of age-related changes in CD4 (L3T4) and CD8 (Lyt-2) determinants of spleen and thymus cells was assessed by fluorescence-activated flow cytometry. Cells from mice ranging from 5 weeks to greater than 2 years of age were examined. There is little age-related change in the proportion of CD4+ CD8- splenocytes in A, C57BL/6, DBA/1, DBA/2, and SJL mice (slopes 0.04, 0.06, 0.08, 0.17 and 0.17, respectively, when age in weeks was plotted against % of positive cells). Changes in the composition of the thymus are much more profound: CD4+ CD8+ cells of SJL mice decrease from 70% to less than 10% as the animals age from 5 to 69 weeks (slope -1.03), and in DBA/2 mice from 5 to 110 weeks (slope -0.88). While this decrease in CD4+ CD8+ cells occurs, there is a compensatory increase in CD4+ CD8- and CD4- CD8+ cells; this is a shift in the relative proportion of subpopulations rather than an increase in absolute cell numbers of a particular subpopulation. In contrast to the age-related changes of SJL and DBA/2 mice, there is relatively little change in the proportion of CD4+ CD8+ thymus cells in mice of strains C57BL/6, DBA/1 and A (slopes -0.03, -0.14 and -0.15, respectively).
Aging↗
Fluorescence-activated cell sorter (FACS) analysis of rabbit cells.
Monoclonal antibodies RB1, RB2, RT1, RT2 and RB3 were prepared against rabbit lymphoid cells by immunization with various fractions of rabbit lymphoid cells. The antigens detected by the antibodies are found on B and T cells in different densities. High proportions of polymorphonuclear and bone marrow cells which do not carry the RABELA and RTLA antigens carry the antigens of the RB and RT series. A subpopulation of appendix sIg-negative, RTLA-negative cells has a relatively high concentration of RT2. In general, B and T cells of the appendix show relatively small differences in the membrane densities of RB and RT antigens.
Animals↗
Cross-reaction of a monoclonal antibody to human MHC class II molecules with rabbit B cells.
Monoclonal antibodies, 21w4 and 44H10, against human MHC class II determinants, were analysed for their reactivity with rabbit lymphoid cells. Both MAb bind to all human B lymphoblastoid lines, irrespective of their HLA-DR phenotype. HLA-DR antigens, purified by affinity to 21W4 IgG Sepharose, can be precipitated with 44H10 MAb, indicating that both antibodies react with the same molecules. Competitive inhibition studies with purified MAb IgG show that 44H10 and 21w4 recognize different epitopes of HLA-DR molecules. The 21w4 MAb, previously shown to cross-react with cells of pig, mouse and sheep, does not react with rabbit lymphoid cells. The 44H10 MAb binds to lymphoid cell suspensions prepared from rabbit appendix, spleen and mesenteric lymph nodes. Its reactivity correlates with that of RABELA, a polyclonal antibody specific for rabbit B cells. Mesenteric lymph node and spleen cell suspensions, depleted of sIg+ cells, are devoid of 44H10+ cells, while similarly-treated appendix B cells still contain a subset of B cells which are sIg-, RABELA+ and 44H10+. These studies thus report on the presence of MHC class II determinants on rabbit B cells, cross-reacting with human HLA-DR.
Animals↗
Regulated systemic activation of rat plasma prorenin.
Nephrectomized rats have above-normal plasma prorenin levels, presumably of extra-renal origin, but essentially no renin, suggesting a lack of "convertase" for prorenin activation. Adrenalectomized rats have low plasma prorenin levels accompanied by high renin activity, suggesting enhanced prorenin activation by the action of a stimulated "convertase" mechanism. Cross-circulation between adrenalectomized and nephrectomized rats for 15 or 30 minutes, dramatically lowered prorenin and raised renin levels in both types of rats, suggesting extensive activation of prorenin to renin. Similarly, in vitro mixing of these bloods (without cross-circulation) raised renin activity over five times the expected calculated level, while prorenin essentially disappeared. In both cases, prorenin from nephrectomized rat plasma apparently was activated to renin by the enhanced action of "convertase" in the adrenalectomized rat plasma. This newly generated renin activity was, like normal plasma renin, almost completely inhibited by a monoclonal antibody against hog renin and generated an immunoreactive angiotensin I. In contrast, cross-circulation or in vitro mixing of blood from normal control and nephrectomized rats produced little detectable activation of prorenin and only modest increments of renin, suggesting relative inactivity of the "convertase" mechanism in normal plasma. Our data suggest that activation of plasma prorenin is a significant regulated pathway for renin production, as it is greatly stimulated after adrenalectomy and deficient after nephrectomy, thereby implicating the kidney as an important contributor to the "convertase" mechanism operating within the circulation.
Adrenalectomy↗
The rabbit immune system: cells regulating the proliferative response of purified T cells to concanavalin A and phytohaemagglutinin.
T cell specific, B cell specific and Ia specific polyclonal antisera, as well as monoclonal antibodies, were employed to characterize cells involved in regulation of T cells, proliferating upon stimulation with concanavalin A or phytohaemagglutinin. Evidence for Ia+ accessory cells was obtained and the constellation of membrane antigens was determined by cytotoxic cell kill with the above mentioned antibodies. Help given by Ia+ cells was not blocked by polyclonal antibody against Ia, in the absence of complement. There was indirect evidence that a fraction of helper/accessory cells were Ia-.
Animals↗
Characterization of rabbit cells by monoclonal and polyclonal antibodies.
Reagents for the identification of rabbit cell markers have been developed at a relatively slow rate. In this paper, rabbit cells are being characterized by polyclonal antibodies against a T-cell antigen (RTLA), a B-cell antigen (RABELA) and an analogue of murine Ia antigen. A number of monoclonal antibodies, specific for lymphocytes and/or bone marrow and/or polymorphonuclear leucocytes, have been used for the analysis of cells with identifiable membrane antigens. Populations that have cells with two of the above antigens in the membranes were identified. To these ends, complement-mediated cell kill by antisera alone and in mixtures was employed.
Animals↗
T cell antigens and MHC determinants on rabbit granulocytes.
A cell preparation, consisting of 90% granulocytes (polymorphonuclear leukocytes), can be obtained from the rabbit peritoneal cavity. These cells have some membrane antigens, similar to those characteristic of thymus cells (T1, T2), but they do not have the thymus antigen, RTLA. Unlike thymus cells, many polymorphonuclear leukocytes have Ia antigen, in their membranes. Heterogeneity of the cell population is indicated by differences in the number of cells affected by complement-mediated cytotoxic cell-kill with monoclonal antibodies, directed against T1 and T2 and with polyclonal antibodies directed against Ia.
Animals↗
Studies of rabbit testes infected with Treponema pallidum. I Immunopathology.
Rabbit testes were injected with suspensions of Treponema pallidum, washed T pallidum, heat killed T pallidum, or Reiter treponemes. The testes were removed three to 24 days after injection and examined for the number of treponemes, the presence of treponemal antibodies, histopathological changes, and presence of T and B cells. In animals infected with T pallidum a substantial number (10(6)-10(7)/ml) of organisms were still present at day 24 in spite of early local production of antibodies and increasing infiltration with plasma cells, T lymphocytes, and macrophages. In animals infected with washed T pallidum a lower degree of inflammation was observed than in those infected with unmodified T pallidum, and the treponemal antibodies were detected simultaneously in samples of testicular fluid and serum. In the groups injected with heat killed T pallidum and Reiter treponemes no macroscopical or microscopical changes were detected, although in the group injected with heat killed T pallidum treponemal antibodies were detected in the testicular fluid on day 24.
Animals↗
A comparison of regulatory cells from rabbit spleen and appendix.
Both spleen and appendix of the rabbit contain two types of accessory cells that regulate the response of T-cells to concanavalin A. These accessory cells are found among non-T, non-B adherent cells and among B-cells. There is, so far, no evidence for a sequential interaction of these two cell types. In addition, there is an inhibitory adherent cell type in the appendix that interferes with the B-cell-regulated proliferative T-cell response.
Animals↗
Rabbit spleen B lymphocytes as helper cells in lymphocyte activation by concanavalin A and phytohaemagglutinin.
Using rosetting methods, we have purified rabbit B cells and studied their interactions with T cells purified by passage over an anti-immunoglobulin-coated Degalan beads column. B cells enhance the response of T cells to concanavalin A (Con A) and phytohaemagglutinin. In regulation of the response to Con A, an adherent cell is a third participating cell. B-cell preparation contain a minority of cells that can respond to T mitogens with the help of non-proliferating T cells, but the proportion of these responding cells is small, and the involvement of the T-cell impurity cannot be excluded.
Animals↗
Allotype and charge-related differences in the immune response.
Rabbits homozygous at the Ab kappa chain allotypic locus (Ab4/Ab4 and Ab9/Ab9) were immunized with negatively and positively charged antigens. The negatively charged antigens were bovine serum serum albumin (BSA; pI = 4.9), ovalbumin (OV; pI = 4.9) and two synthetic polypeptides: copolymer L-glutamic acid L-tyrosine (abbreviated TG; pI = 4.8) and multichain poly (L-tyrosine: L-glutamic acid) poly D-alanine: poly L-lysine (poly L-lysine backbone) abbreviated (TG) --AL; pI = 4.8). The positively charged antigen was hen egg lysozyme (LYS; pI = 10.2). Homozygous Ab9 rabbits responding to negatively charged antigens made less antibody than did Ab4 homozygotes. In contrast, both groups of animals responded equally well to positively charged lysozyme. The relative electric charges of the antibodies were assessed by Sephadex A-50 chromatography. The charge distribution was found to depend on the charge of the eliciting antigen. The positively charged antibodies of Ab9/Ab9 rabbits were not nearly as positively charged as those raised in Ab4/Ab4 rabbits. The difference in average electric charges and in the range of these charges between Ig Ab4 and Ig Ab9 explain quantitative differences in antibody formation in response to negatively charged antigens and may be a contributing factor to the "pecking order", i.e. unequal phenotypic expression of light chain genes in Ab4/Ab9 heterozygotes.
Animals↗
Basilea kappa light chains of rabbit immunoglobulins.
Immunogenetics of the Basilea allotype were investigated. It was shown that the Basilea gene is controlled at a locus identical with, or closely linked to, the Ab kappa allotypic locus. Basilea-positive molecules have been physically separated by immunoabsorption from molecules carrying the lambda chain markers, c7 and c21. Injection of newborn Basilea homozygotes with anti-Basilea immune serum results in suppression of the synthesis of Basilea-positive molecules, but does not affect the synthesis of the lambda chain, or of the heavy chain allotypic markers. Allotype-suppressed Basilea homozygotes do not recognize either the Basilea allotype or the kappa isolate as 'self' and make anti-Basilea and anti-kappa antibody upon immunization with Basilea antigen. The specificity of this antibody was identical with that of a heterologous anti-kappa immune serum raised in a goat and made specific by absorption with purified lambda material. These results prove that Basilea gene products are of kappa isotype and are controlled at the Ab allotypic locus.
Animals↗