Katsuiku Hirokawa

Role of the Thymus in Aging of the Immune System

The age-related decline of immune functions has been well documented in humans and rodents, although the onset, magnitude, and rate of the decline are different depending on species, strains, and immunological indices. There has been accumulating evidence that the age-related decline of immune functions is due mainly to T-cell insufficiencies caused primarily by an early decline in thymic function (Makinodan et al., 1987; Hirokawa, 1985). This chapter attempts to describe the mechanism of the age-related thymic involution and its influence on the aging immune system.

Immunopathological Analysis of Interstitial Renal Lesions in Elderly People

The incidence of focal lymphoid infiltrates in the renal interstitium was examined in autopsy cases of young and old subjects, and the infiltrating lymphocytes were immunohistologically characterized by a panel of monoclonal antibodies. Histologically, 198 and 227 autopsy cases over 60 years of age (87.2%) were shown to have mononuclear cell infiltrates of varying degree in the renal interstitium, whether or not these were accompanied by progressive arteriosclerotic changes. Above all, severely infiltrating foci in the renal interstitium were frequently found in the elderly over 70 years of age overlapping arterio-artherolosclerotic changes. In contrast, in the 54 younger control subjects under 49 years of age, the incidence of such a lesion was less (5.6%). An immunohistologic study revealed that the infiltrating mononuclear cells were predominantly composed of CD4+ cells, whereas CD22+ B cells were apparently lesser in number. Moreover, a considerable proportion of T cells was activated as judged by IL-2 receptor expression. From these findings, we now propose that susceptibility to the development of interstitial renal lesions in the elderly involves the cellular immune response, and may be related to an age-associated disturbance in regulatory T-cell function.

Immunopathological Study of Neuropeptide Expression in Human Salivary Gland Neoplasms

The immunoreactivity of anti-neuron-specific enolase (NSE) and anti-Leu-7 on formalin-fixed sections of human salivary gland neoplasms was determined by the avidin-biotin-peroxidase complex method. In addition, neuropeptides, such as vasoactive intestinal polypeptide, somatostatin, and substance P, in human salivary gland neoplasms were expressed, whereas other polypeptides, including glucagon, cholecystokinin, leu-enkephalin and calcitonin, were absent. When 182 paraffin-embedded examples of human salivary gland tumors, including 112 benign and 70 malignant neoplasms, were examined immunohistochemically, positive immunoreactivity was observed in: 51 cases with NSE (59%) and 46 cases with Leu-7 (54%) of 86 pleomorphic adenomas; 11 cases with Leu-7 (61%) of 18 Warthins tumors; 7 cases with Leu-7 (58%) of 12 acinic cell carcinomas; 5 cases with NSE (31%) of 16 adenoid cystic carcinomas; 5 cases with NSE (42%) and 4 cases with Leu-7 (33%) of 12 adenocarcinomas; 4 cases with NSE (25%) and 6 cases with Leu-7 (38%) of 16 undifferentiated carcinomas. The other tumors, such as oxyphilic adenomas, basal cell adenomas, epidermoid carcinomas, and mucoepidermoid carcinomas, were nonreactive. Neuropeptides were observed in the neoplastic epithelial cells of certain tumors such as Warthins tumors, acinic cell carcinomas, adenocarcinomas and undifferentiated carcinomas. These findings suggest the possibility that cells of neuroendocrine origin, present in certain neoplastic salivary gland epithelia may play a significant role in the histogenesis of human salivary gland neoplasms.

Autoimmune sialadenitis: possible models for Sjögren's syndrome and a common aging phenomenon.

This article will review recent observations of autoimmune sialadenitis as it occurs in murine systems, in human Sjogrens syndrome, and in aging process. Analysis will be focused on their histologic, immunologic, immunopathologic and serologic abnormalities

Assessment of Age-related Decline of Immunological Function and Possible Methods for Immunological Restoration in Elderly

The immune system plays an important role in protection against infection and in the maintenance of the internal environment of the body. However, such important immune functions are known to decline with age in many mammals, including humans. It is a matter of clinical importance that the incidence of various age-associated diseases such as infections, cancer and vascular disorders increases with a decrease in immunological vigor. The extent of immunologic decline is variable and exhibits wide inter-individual variations. Thus, it is important to assess the extent of immunologic decline in both patients suffering from various diseases and in healthy people in order to maintain healthy conditions. To this end, we have developed a scoring system that analyzes immune parameters according to a database of known age-associated immune changes obtained from a healthy population. Using this scoring system, we can combine several different immunological parameters and express the immune status of individuals as a simple numeral. After determining immunological vigor for individuals, it is necessary to replenish immune defects and restore them to normalcy for individuals with depressed immunological scores. This chapter provides methods of immunological restoration in animal models and introduces some similar attempts in humans. The effect of any immunological restoration varies with the individual and must therefore verified. Currently, the proposed immune scoring system proposed is useful to determine whether the methods employed are effective for the restoration of immune functions.