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Biomedical subjects

B Cinader

Publications and source records attributed to B Cinader.

At least 55 records · Page 3Linked to original sources

Expression of IL-2 receptors on peripheral blood lymphocytes from young adult and aged human donors.

Peripheral blood mononuclear cells from young adult and aged human donors were activated with PHA and the expression of IL-2 receptors was examined. For the detection of IL-2 receptor-positive cells, flow cytofluorometry using monoclonal antibody Clonab IL-2R, fluorescein-conjugated swine anti-mouse IgG and fluorescence activated cell sorter FACS 440 were utilized. The age-related decrease in the expression of IL-2 receptors was observed: the percentage of IL-2 receptor-positive PBMC was substantially higher in the group of young adult donors than in the group of the aged individuals.

Adult↗

Age-related changes of beta-adrenoceptors in spleen lymphocytes and cerebral cortex of NZB/BIN mice.

The density (Bmax) of beta-adrenoceptors in splenic lymphocytes of NZB/BIN mice decreased up to an age of about 40 weeks and then levelled out. The Bmax in cerebral cortex, on the other hand, increased in the first half of life and then changed relatively little. The dissociation constant of the ligand (Kd) was larger in the cortex than the spleen and showed relatively little age-dependent change.

Aging↗

Age- and strain-dependent polymorphism in IgE antibody against the phosphorylcholine hapten.

The magnitude of the IgE antibody response against the phosphorylcholine (PC) hapten and the rate of age-related change of IgE formation is polymorphic in the three long-lived and six relatively short-lived strains of mice studied. Long-lived mice showed an early increase, followed by a decline in the levels of anti-PC IgE antibody. The rate of increase and decrease was strain dependent. Among short-lived strains, MRL/Mp-lpr and MRL/Mp-+ mice showed an early decline in IgE antibody. The extent and rate of decline with age was more rapid in MRL/Mp-lpr animals than in MRL/Mp-+ mice. In contrast, there was an early increase of IgE antibody in female SJL, NZB/BIN, BXSB/Mp and male BXSB/Mp. Thus, opposite age-related changes in IgE antibody production can occur in animals with a tendency to develop autoimmune disease. In hybrids of (SJL X BALB/c)F1 and (BALB/c X MRL/Mp-lpr)F1, the levels of IgE antibodies were higher than those observed in either parental strain, and declined steeply with advancing age. We suggest that this could be attributed to recessive inheritance.

Aging↗

Isotype-specific resistance against tolerance induction in SJL mice.

Age-related changes in antibody response of SJL mice were examined in terms of isotype expression after treatment with immunogen or with immunogen, preceded by the molecule in normally tolerogenic form. We report here that tolerance induction and resistance to down regulation are isotype specific. Tolerance can be induced in terms of all detectable isotypes at the age of 5 weeks. In older SJL mice, tolerance to the carrier is found in IgM antibody, whereas there is resistance against down regulation in terms of IgG2a and IgG2b isotypes, and sensitization in terms of IgG3, IgG1, and IgA antibody. Furthermore, the degree of down regulation is determinant dependent. This was observed when older SJL mice, pretreated with the carrier in a normally tolerogenic form, were immunized with haptenated carrier and tested for their response to hapten and carrier determinants. In this case, IgA antibody shows tolerance to the hapten and sensitization by carrier determinants.

Animals↗

Polymorphism of age-related changes in stimulatory capacity of murine dendritic cells.

All through life, regulatory and executive components of the immune system undergo changes, differing in rate and extent, dependent on the genetic background. We have, here, examined age-dependent changes in stimulatory capacity of dendritic cells (DC) in allogeneic mixed leukocyte reaction (MLR). DC of mice of five strains showed very little change as they aged. DC from mice of two other strains showed a significant age-related decrease of stimulatory activity and those of one strain showed an increase. The capacity of DC to stimulate syngeneic MLR was examined in three strains, as a function of age, and was found to decrease in one and to slightly increase in two. The underlying cause for this extensive polymorphism remains to be determined. We could not find supporting evidence for the view that the observed changes were related to changes in Ia density on dendritic cells.

Aging↗

Age-related decrease in ultraviolet induced DNA repair in neurons but not in lymph node cells of inbred mice.

DNA repair capacity was measured, as UV induced, unscheduled DNA synthesis (UDS), in cells of the nervous and immune system of three mouse strains, as a function of age. The strains examined were DBA/1J, C57B1/6J and SJL/J. For dorsal root ganglion neurons of strain DBA/1J, aged 97-98 weeks, a significant decline in UDS of 53% at 20 J/m2 and 73% at 40 J/m2, respectively, was measured, when compared to mice aged 17-18 weeks. Similarly, neurons from C57B1/6J mice, aged 115-116 weeks, showed significant, age dependent decreases of 31% at 20 J/m2 and 40% at 40 J/m2, respectively, compared to mice aged 7-8 weeks. In lymph node cells of all three strains employed, no significant age related decreases in UDS were detected. While the complexity of processes involved in DNA repair makes conclusive interpretation of the results precarious, the results obtained for post-mitotic cells of the nervous system, may be viewed as compatible with the DNA repair hypothesis of ageing.

Aging↗

Dietary fat alters progression of some age-related changes of the immune system.

SJL mice develop resistance against tolerance between the 9th and 25th wk of life. This resistance is linked with a loss of suppressor capacity in the thymus. We have shown here that contact photosensitivity (CPS) decreases as a function of age and that this is due to an age-dependent increase in suppressor capacity. Diet fats have a differential effect on age-dependent changes in suppressor activity; a low P/S diet prevents or delays loss of suppressor activity for antibody formation and a high P/S diet prevents or delays the development of suppressor activity in CPS reactions.

Aging↗

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↗

Age-related changes in beta-adrenoceptors of lymphocytes.

The density of adrenoceptors (Bmax) is greater on B than on T splenocytes. It decreases more or less rapidly on membranes of both populations, as animals age. The exception, we have observed in this respect, is an increase in Bmax on B cells of SJL mice, between the 6th and 25th week of life.

Aging↗

Changes in lymphoma development in female SJL/J mice as a function of the ratio in low polyunsaturated/high polyunsaturated fat diet.

A diet of low polyunsaturated-to-saturated fatty acid (P/S) ratio known to alter fatty acid composition of lymphocyte membranes and retard the progressive changes which result in loss of suppressor capacity in SJL/J female mice, was fed to these mice from conception to study its effect on the development of lymphoma. Between 12 and 14 months, at a time when 100% of mice on a diet of high polyunsaturated-to-saturated fatty acid ratio showed lymphoma, only 70% of the mice fed the low P/S diet had developed lymphoma. Dietary fatty acid levels would appear to have a significant effect on the rate of progression of lymphoma in SJL/J female mice.

Animals↗

Age-related changes of beta-adrenoceptors in aging inbred mice.

The density (Bmax) and antagonist dissociation constant (KD) of beta-adrenoceptors were determined on spleen and brain of three different inbred strains of mice--BALB/cJ, C3H/HeJ, and C57BL/6J. Receptor densities (Bmax) differed with strain and declined in both spleen and cortical receptor populations as mice became older. Age-related changes in KD were found on spleen cells of BALB/cJ and in the cortex of C3H/HeJ and C57BL/6J. Bmax and KD in different organs of the same strain changed at different rates. changed at different rates.

Aging↗

Functional competence of dendritic cells of ageing C57BL/6 mice.

Highly polymorphic age-dependent differences in progression of T and B cells have been found in various strains of inbred mice. In the immune system of C57BL/6 mice these occur first in B cells and, later in life, in T cells. In this paper, we have examined the progression in the functional capacity of C57BL/6 dendritic cells (DC). Age-dependent changes were found in the syngeneic mixed leucocyte reaction, in which the stimulatory capacity of DC increased with age. This increase was independent of the age of the donor of the serum that was added to the culture, and occurred when young donors provided the T cells. Age-dependent changes in DC properties were not detected in terms of direct plaque-forming response, response to concanavalin A, or in the allogeneic mixed leucocyte reaction.

Aging↗

Differentiation of regulatory cell interactions in aging.

Age-related changes in different regulatory processes are polymorphic and differ in different strains and organs in terms of onset and progression. Membrane changes have been observed in terms of the association between receptors and class I major-histocompatibility-complex molecules as well as in terms of structural modification of membrane molecules. Various nutritional strategies can differentially affect age of onset and rate of progression. Tumor incidence and progression increase with age; and interesting exception has been described. Principles of experimental design for the exploration of aging processes and evolutionary aspects of aging processes are being discussed. Identification of alleles, which affect initiation and progression of deleterious aging processes, are being considered for their potential in strategies for preventive medicine.

Aging↗

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↗

Strain-dependence and cellular aspects of the acceleration of age-dependent shift in class-specific helper and suppressor activity in the thymus of MRL/Mp mice by the LPR gene.

Previous studies of the immunoregulatory activity of thymocytes from SJL/J mice have shown loss of suppressor activity for the antibody response by 24 weeks of age with appearance of helper activity. At the same time, suppressor cells developed which inhibit the generation of cytotoxic T lymphocytes (CTL). We now show a similar pattern of helper and suppressor activity in MRL/Mp mice. Presence of the lpr/lpr genotype significantly accelerated the onset of these changes in thymocyte activity. A similar pattern of thymocyte activity was not detected in C57B1/6 mice. In aged MRL-lpr mice, evidence of increased suppressor cell activity for the CTL response could be demonstrated in spleen, and the suppressor was sensitive to treatment with anti-thy 1.2 + complement. The magnitude of the deficiency in the CTL response in MRL-lpr mice was greater than could be accounted for by suppressor cell activity alone. Measurement of the frequency of CTL precursors (CTLP), the yield of CTL per CTLP, and the ability to produce and to respond to interleukin 2 (IL-2) indicated that a drop in CTLP frequency, subnormal generation of IL-2, and probably an intrinsic defect in the responsiveness of MRL-lpr CTLP to IL-2 was contributing to the defective CTL response. We were not able to link suppressor T cells with reduced responsiveness to IL-2. Ageing involves different patterns of change in immunoregulatory T-cell subsets in different strains of mice, depending on their genetic constitution. The general implications of this conclusion for prediction of immune dysfunction with age in genetically distinct members of an outbred population are discussed.

Aging↗

Immune response, tolerance circumvention and autoantibodies in aging MRL/Mp-lpr and MRL/Mp-+ mice.

Isotype distribution was analyzed, as a function of age in MRL/Mp-lpr and MRL/Mp-+ mice. The mice were tested for: (1) "spontaneous" response to nucleic acid (2) induced response to alum-precipitated phosphorylcholine-rabbit gamma globulin (PC-RGG) (immunized animals) and (3) induced response to alum-precipitated PC-RGG after pretreatment with aggregate-free RGG (tolerized-immunized animals). "spontaneous" nucleic acid antibodies of isotypes, other than IgM, increased as animals became older. The quantity of RGG antibody declined as a function of the age at which animals were immunized. Young tolerized-immunized animals made less antibody of all isotypes than did immunized animals. In later life, resistance against tolerance induction developed. Aggregate-free RGG sensitized older animals and, thus, augmented the response to alum-precipitated PC-RGG. Up to the age of 20 weeks, spontaneous antibody and antibody of tolerized-immunized animals showed striking similarities in age- and strain-dependent changes of IgG2b and IgA isotypes. Results were discussed in terms of: (1) a defect in down regulation of immune responsiveness, which contributes to the initiation of autoimmunity and age-dependent resistance to tolerance induction; (2) regulatory mechanisms for isotype switching, which contribute to resistance to tolerance induction, whether naturally occurring or experimentally induced; and (3) age-related immunological changes which are inherent in the MRL/Mp genome, the mutant gene, lpr/lpr, accelerating the changes.

Aging↗

Changes of histone H1 subtypes with aging in strains of mice that possess different immunological characteristics.

Relative proportions of histone H1 proteins were determined for brain, heart, liver, and spleen for five strains of mice as a function of age. The strains examined were SJL/J and MRL/MPJ-lpr/pr which develop early resistance to tolerance and A/J, C57BL/6J and MRL/MPJ-+/+ which do not. Heart, brain, and liver of most of these strains displayed significant relative increases in histone H1(0) and coordinate decreases in H1I or H1II with age. In contrast, spleen cells, which are highly proliferative, contained little or no histone H1(0). Only spleen cells from a mouse strain with a predisposition to lupus erythematosus, MRL/MPJ-lpr/lpr, displayed any significant H1 changes.

Aging↗