Search PubMed⌕ Search

Biomedical subjects

T Makinodan

Publications and source records attributed to T Makinodan.

At least 19 recordsLinked to original sources
PubMed1991

Cellular immunosenescence: an overview.

Recent studies on space flights suggest that certain T cell immunologic activities are vulnerable to microgravitation. It would be desirable to know the extent to which these changes can be prevented or reversed. Since the changes observed are analogous to the effects of aging on immunity, a brief overview is presented of our current knowledge of age-related changes in immune cells and of the various interventional methods which have been used successfully in preventing the decline with age and in elevating the levels of immune functions of old individuals.

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↗
PubMed1975

Thymic involution: effect on T cell differentiation.

The thymus of long-lived BC3F mice involutes progressively throughout life, beginning at 6 weeks of age. This is manifested by the loss of cortical lymphoid mass and by the degenerative changes in epithelial cells. The purpose of this study was to determine to what extent age-related degenerative changes of the thymus affect its capacity to influence the maturation of thymic-derived (T) cells. Accordingly, thymic lobes of mice ranging in age from 1 day to 33 months were implanted under the kidney capsule of T cell-deprived syngeneic young adult TXB mice, and the emergence of T cells was assessed kinetically by various morphologic and functional indices which may be reflective of different T cell subpopulations. They are: a) histology of the thymsu graft, b) lymphocyte repopulation of the T cell-dependent areas of lymph nodes, c) total number of splenic lymphocytes carrying theta antigens (theta-+), d) T cell-dependent humoral immune response and e) proliferative response of splenic cells to plant lectins, phytohemagglutinin (PHA) and succinyl-concanavalin A (s-Con A), and allogeneic lymphocytes. The results revealed that the T cell-transforming influence of thymic tissues generally decreases with increasing age. The difference in the patterns of recovery of the various indices of thymus-grafted TXB mice suggests that the extent to which T cells can mature is dependent upon the degree of involution the thymic tissue has undergone with age. In particular thymic tissues lose the capacity to influence the following functions with advancing age: 1) lymphocyte repopulation of the T cell-dependent areas of lymph nodes; 2) mitogenic reactivity of splenic cells to T cell-specific mitogens (PHA and s-Con A): 3) number of splenic theta-+ lymphocytes and splenic T cell helper function; and 4) mitogenic reactivity of splenic T cells to allogeneic lymphocytes.

Aging↗
PubMed1975

Immunodeficiency and autoimmunity in aging.

In general, both cell-mediated and humoral immune activities decline with advancing age and, associated with this decline, is an increase in the incidence of certain types of autoimmune disease, cancer and infection. Not only may the relationship be causal, but the former may be a significant factor involved in the expression of the latter. Discussion is focused primarily on the relative contribution of extrinsic and intrinsic factors responsible for the immunodeficiency of aging individuals.

Aging↗
PubMed1975

Effects of aging on the differentiation and proliferation potentials of cells of the immune system.

An attempt has been made here to show that the immune system can begin to decline in function shortly after an individual reaches maturity. The decline is due in part to changes in the environment of the cells but primarily to changes in the precursor cells of the system. This is reflected in their inability to proliferate and possibly differentiate efficiently. These findings show that the immune system can serve as an excellent model to study how aging can perturb the process of cells undergoing proliferation and differentiation.

Aging↗
PubMed1975

Effect of age on cell-mediated immunity in long-lived mice.

The cytolytic ability of sensitized spleen cells to kill allogeneic target cells in vitro, a correlate of cell-mediated immune activity, was assessed in aging long-lived hybrid mice. There was about a 4-fold decline with age, of which about 2-fold could be accounted for by the decrease in relative numbers of immunocompetent precursor cell units. The terminally differentiated progeny cells of antigen-stimulated precursor cells of old mice were as efficient in killing target cells as were those of precursor cells of young mice. Thus, it would appear that a decrease in the proliferative and transforming capacities of antigen-stimulated precursor cells of old mice can account for the other 2-fold decline with age in the cytolytic activity. Cytolytic activity may not be the limiting function in resistance to tumour formation. This was indicated by the observation that resistance to allogeneic tumor cell challenge declines with age by as much as 500-fold in mice, showing only a 4-fold decline in their cytolytic activity.

Aging↗
PubMedDate not supplied

The late effects of selected immunosuppressants on immunocompetence, disease incidence, and mean life-span. I. Humoral immune activity.

The effect of different immunosuppressive treatments during young adulthood or humoral immune competence late in life was determined. It was found that the marked reduction in humoral immune competence in aged mice is further compromised when severe insults are administered early in life. Thus, thymectomy, splenectomy, and sublethal X-irradiation produced lasting immunodepression as measured (1) in situ and (2) by the hemolysin, direct and indirect plaque forming cell responses of adoptively transferred spleen cells. In contrast, treatment with cyclophosphamide and cortisone acetate were without effect, indicating that drug-damaged cells of the immune system were replaced by competent cells during the course of time. Decrease in immune competence of aged thymectomized animals could not be correlated with a decrease in numbers of theta-bearing T or immunoglobulin receptor-bearing B lymphocytes. The significance of the observed unequal effects of these immunosuppressants on immune competence, as they relate to disease incidence and life expectancy, are dealt with in the third paper in this series.

Age Factors↗