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Biomedical subjects

T Makinodan

Publications and source records attributed to T Makinodan.

At least 91 records · Page 5Linked to original sources
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↗
PubMed1972

Model approach to immunological rejuvenation of the aged.

Reconstitution of a damaged or exhausted immune system by injection of genetically compatible immunocompetent cells (immunologic rejuvenation) is a promising approach for restoration of immune activity. By using this model, spleen cells from young-adult mice, previously immunized with Salmonella typhimurium, were transferred to either young-adult or old, syngeneic recipients before or after storage at -196 C. The susceptibility of recipient mice was then determined by challenging them at increasing time intervals after reconstitution with lethal doses of the virulent organisms. The findings, although preliminary in nature, demonstrate that (i) immunological rejuvenation of mice is possible with immunocompetent cells from specifically immunized donors; (ii) prolonged "takes" of these cells can occur even in nonirradiated recipient mice, and (iii) storage at -196 C does not impair their protective capacity.

Aged↗