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T Makinodan

Publications and source records attributed to T Makinodan.

At least 73 records · Page 4Linked to original sources
PubMed1980

In vivo evaluation of age-associated changes in delayed-type hypersensitivity.

The effectiveness of a recently developed isotopic in vivo assay for the measurement of delayed-type hypersensitivity (DTH) was compared to that of the conventional skin sensitization assay based on the ear-swelling index. DTH was measured in young and old C57BL/6 mice under conditions of normal health, spontaneous reticular cell sarcoma, Sendai virus infections and under the above conditions, while being treated with a potential immunorestorative agent, mercaptoethanol. A good correlation was observed between the two types of assay. However the reliability and sensitivity of the isotopic assay was found to be superior to the conventional skin sensitization assay. Thus, under optimum conditions, the swelling assay showed a 35% decline in DTH in old mice, and the isotopic assay a 62% decline.

Aging↗
PubMed1980

Restoration of impaired immune functions in aging animals. IV. Action of 2-mercaptoethanol in enhancing age-reduced immune responsiveness.

The enhancing effect of 2-mercaptoethanol (2-ME) on the immune responses of young and old unseparated spleen cells and purified populations of T-cells, B-cells and macrophages was studied. While 2-ME enhances both the normal responses of young cells and the age-reduced responses of old cells, the sulfhydryl compound has a relatively greater enhancing effect on old spleen cells in the humoral response to sheep red blood cells and the blastogenic response to concanavalin A (Con A). The greater enhancing effect in the humoral response appears to be due to 2-ME overcoming a suppressive effect of old T-cells which develops with increasing age. The greater enhancing effect in Con A stimulation appears to be an effect on the Con A responsive sub-population of T-cells and not on the synergistic effect of the presence of B-cells.

Aging↗
PubMed1979

Restoration of impaired immune functions in aging animals. II. Effect of mercaptoethanol in enhancing the reduced primary antibody responsiveness in vitro.

The enhancing effect of 2-ME on the in vitro primary antibody forming capacity of young and old spleen cells from 5 different strains and hybrids was investigated by assessing the number of antibody-forming cells in response to sheep RBC stimulation. The following results were obtained: (1) the optimum concentration of 2-ME is 5 x 10(-5) M; (2) the best time to expose cultures to 2-ME is on day 0 together with the antigen, although days 3 and 4 were equally as effective with young but not old spleen cells; (3) 2-ME can enhance slightly the time of peak antibody response, but this appears to be strain dependent; (4) in response to antigenic stimulation over a 10,000-fold range in antidgen dose, antibody response by cultures exposed to it; (5) 2-ME is comparable to, or better than, those which had been exposed to it; (5) 2-ME is effective in enhancing antibody response because it probably promotes proliferation and transformation, as well as protects dividing cells which otherwise could not survive the culture conditions; (6) the relative number of viable cells detected on the third day of culture after antigen stimulation can be used in predicting with a reasonable accuracy (pie 2, 0.94) the magnitude of peak antibody response, which is detected normally about 2 days later; (7) 2-ME enhances antibody response of young spleen cells by about 30%, but is quite variable depending upon the genetic strain, varying from a low of --20% with random bred CV1 cells to a high of 100% with inbred C57B1 cells; (8) the enhancing effect of 2-ME on old spleen cells is much more impressive, being more that 10 times greater than on young spleen cells (i.e., 500 vs. 30%), although it too is quite variable, ranging from a low of 85% with C3H cells to a high of about 1100% with C57BL cells; (9) the enhancing effect of 2-ME on limiting numbers of spleen cells is most impressive, as judged by the relative magnitude of response by limiting (3 x 10(6)) and optimum numbers (10 x 10(6)) of young and old spleen cells and by the frequency of antibody response of cultures with limiting and optimum numbers of cells exposed to 2-ME was 23 and 3 times greater than that not exposed to 2-ME, respectively; and with old spleen cells, it was 30 and 12 times greater. In terms of the frequency of antibody responding cultures with limiting numbers of young spleen cells (3 x 10(6)), 77% responded in absence of 2-ME, whereas 100% of the cultures responded in the presence of 2-ME. The effect of 2-ME on cultures containing limiting numbers of old spleen cells was much more striking, for, in contrast to only 9% of the cultures responding in the absence of 2-ME, 78% responded in the presence of 2-ME.

Age Factors↗
PubMed1979

Restoration of impaired immune functions in aging animals. III. Effect of mercaptoethanol in enhancing the reduced primary antibody responsiveness in vivo.

The enhancing effect of 2-ME on the primary antibody forming capacity of young and old mice from 5 strains and hybrids was investigated by assessing the number of hemolytic antibody-forming spleen cells in response to sheep RBC stimulation. The following results were obtained: (1) the optimum dose of 2-ME is 4 micrograms per mouse; (2) the best time to administer 2-ME is just prior to, or at the same time as, antigen is given; (3) 2-ME can enhance response to suboptimum and optimum, but not supra-optimum doses of antigen; (4) 2-ME is effective in enhancing the primary antibody forming capacity of both young and old mice, with one exception, but the enhancement of old mice was greater than that of young mice (80% vs. 20%). The exception was old C57Bl mice, in which 2-ME was ineffective; (5) the level of primary antibody forming capacity of old mice can be restored to that of young mice by treating them with 3--4 weekly injections of 2-ME at a dose of 4 micrograms per injection.

Aging↗
PubMed1979

Control of immunologic abnormalities associated with aging.

In an attempt to encourage more intensive studies on the control of immunologic abnormalities associated with aging, the six different approaches which have been attempted are reviewed briefly. They are as follows: (a) internal body temperature control, (b) tissue ablation, (c) dietary manipulation, (d) genetic manipulation, (d) genetic manipulation (e) cell therapy and (f) chemical therapy. The first four are preventive and the latter two are restorative in approach. Many of these studies are very preliminary, but overall, the findings are most encouraging. These studies should resolve the extent to which decline in immunologic vigor with age influences the disease pattern of aging individuals and on their life expectancy.

Aging↗
PubMed1976

Decline in the growth potential of spleen-colonizing bone marrow stem cells of long-lived aging mice.

The growth capacity of femoral bone marrow stem cells from young and old long-lived mice was assessed in the spleen of X-irradiated young and old syngeneic recpients by determining: (a) the number of stem cells colonizing the spleen, (b) the rate of incorporation of 125I-labeled iododeoxyuridine by proliferating colony cells, and (c) the number of cells present in the largest colonies at the end of the growth phase.We found that the growth capacity of stem cells declined with age. We further found that the spleen-seeking and spleen colony growth capacities of old stem cells remained characteristically old even after they were allowed to self-replicate in the bone marrow of young recipients for an extended period of time. On the other hand, the spleen colony growth capacity of young stem cells could be reduced by allowing them to self-replicate in old recipients. These results suggest that the growth capacity of old stem cells is an intrinsic characteristic which cannot be readily altered, but that of young stem cells can be aged in an accelerated manner by allowing them to self-replicate in old recipients. An additional reduction was noted in the frequency of both young and old stem cells colonizing the spleen of old recipients and in the cell density of the largest colonies produced. These results indicate that factors extrinsic to the stem cells are also responsible for the decline with age in their spleen colony growth capacity.Thus, the growth capacity of old stem cells in old recipients could be as low as 10% that of young stem cells in young recipients.

Aging↗
PubMed1976

Immunobiology of aging.

Normal immune functions can begin to decline shortly after an individual reaches sexual maturity. Although changes in cellular environment are partially responsible, the decline is due primarily to changes within the cells, especially the T cells and to some extent the stem cells. This is reflected in their inability to proliferate and differentiate efficiently. What needs to be resolved is whether the altered properties of T cells and stem cells are permanent or reversible and, if permanent, whether they are due to a stochastic or genetically programmed event. The decline with age in certain normal immune functions is associated with an increase in the frequency of autoimmune and immune complex diseases, certain types of cancer, and viral and fungal infections. These diseases, compromise normal immune functions in short-lived strains of mice. In long-lived mice and in humans, however, the decline in immune functions to threshold levels seems to predispose in individuals to illness.

Aging↗
PubMed1976

Reduced humoral immune activity in long-lived old mice: an approach to elucidating its mechanisms.

Spleen cells from young (3-5 months) and old (22-27 months) mice were assessed in cultures, both in vivo and in vitro, for their anti-sheep RBC response separately and in mixtures. Pooled young spleens, pooled old spleens, and individual old spleens were analysed. The response of pure young spleen cells was always higher than that of pure old spleen cells (approximately 30 times). The responses of mixtures were either less than (i.e. reduced; frequency approximately 65%), comparable to (i.e. additive; frequency approximately 10%), or greater than (i.e. elevated; frequency approximately 30%) the sum of the responses given by equivalent numbers of pure young and pure old spleen cells. The reduced response was observed in mixtures containing cells from histologically normal old spleens, old spleens with tumours and old spleens with atrophic follicles. Additive and elevated responses were observed only in mixutres containing cells from histologically normal old spleens. The reduced response is explicable in terms of excessive numbers of suppressor cells in old spleens that can prevent young immunocompetent cells from responding maximally to the test antigen. The additive response can be accounted for by a reduction in number of immunocompetent cells in old spleens and/or a decrease in their functional efficiency. The elevated response can be explained by a reduction in number of at least one type of immunocompetent cell in old spleens that exists in excess in young spleens. These results indicate that there are several types of cellular changes responsible for the decrease in humoral immune activity in old mice. Pooling of old spleens, as was commonly done in the past, should therefore be discouraged. Not only might it selectively favour the expression of old spleens with an excess of supressor cells but it conceivably could result in an elevated response.

Aging↗