Lymphocyte subsets and integrated immune function in aging humans

Hallgren, Helen M.; Kersey, John H.; Dubey, Devendra P.; Yunis, Edmond J.

doi:10.1016/0090-1229(78)90010-7

Cited by 76 publications

(16 citation statements)

References 16 publications

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“…Increased immunosuppression with aging has been repeatedly reported (32)(33)(34)(35)(36); it has been mainly attributed to increase in the population size of nonspecific B cells (37,38) or T cells (39) while antigen-specific suppressor T cells remain unchanged (39). These findings, however, are in contrast with the observation that concanavalin A-activated lymphocytes from aging humans manifest a loss in the ability to nonspecifically suppress the response to mitogens and allogeneic cells (40) and are in contrast with the age-related decline in suppressor T cell activity either found in NZB mice (41), which are prone to autoimmunity and accelerated senescence, or hypothesized in normally aging mice (28).The inconsistency of experimental observations based on different methodological approaches stresses the need to further investigate whether changes in T cell suppression, which plays a central role in immunoregulation, may account for the progressive deterioration ofthe immune system with advancing age. The present study was undertaken to evaluate age-related alterations of antigen-specific T cell suppression in a well-defined experimental system, the immune response to azobenzenearsonate (ABA), which has been extensively investigated by Nisonoff's and Benacerraf's groups at the level of antibody production and delayed-type hypersensitivity (42).…”

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confidence: 54%

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confidence: 54%

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Immunoregulation in senescence: increased inducibility of antigen-specific suppressor T cells and loss of cell sensitivity to immunosuppression in aging mice.

Doria¹,

Mancini²,

Adorini³

1982

Proc. Natl. Acad. Sci. U.S.A.

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Azobenzenearsonate (ABA)-specific T cell-mediated suppression has been studied in aging mice. ABA-specific suppressor T cells were induced in young and old mice by injection ofABA conjugated to syngeneic spleen cells (ABA-SC). These suppressor cells were tested for their ability to suppress the in vitro anti-trinitrophenyl (TNP) antibody response of lymph node cells obtained from ABA-keyhole limpet hemocyanin (KLH)-primed young or old mice and cultured with TNP-ABA-KLH. Suppressor T cells were found to be more easily induced in old than in young mice but to suppress less efficiently the antibody response of cells from old than from young mice. The increased inducibility of antigen-specific suppressor T cells in old mice is compatible with the age-dependent decline of immune responsiveness to exogenous antigens. The loss of cell sensitivity to antigen-specific immunosuppression as well as the lack of evidence for increased nonspecific suppression in old mice is consistent with the age-related increase in autoimmune disorders. These findings provide a unifying explanation for the most relevant immunological phenomena of senescence.Immunologic mechanisms are involved to a large extent in the biologic processes of aging, as reviewed by Walford (1). The maximal lifespan, which appears to be regulated by a finite set of genes (2), is significantly influenced by the major histocompatibility complex (3), which plays a fundamental role in the genetic control of immunologic functions (4). Morphologic, functional, and pathologic alterations occurring in aging animals are associated with both progressive decline of immune responsiveness to exogenous antigens and increasing incidence of autoimmune phenomena (5).The decline of immune responsiveness results mostly from alterations of lymphoid cell populations rather than from changes in the animal milieu during senescence (6). Number and activity of macrophages seem to be unaffected by aging (7-9). Most reports indicate no or only a slight decrease in lymphocyte number but profound functional defects in B cell and helper T cell populations during senescence (10-17). The decrease in helper activity has been attributed to thymus involution (18) and subsequent reduced concentration ofthymic factors (19-21) involved in the differentiation ofprecursor cells into functionally mature T cells (22).The incidence of autoantibodies in mice and men shows a dramatic increase with age (23). The B cell resistance to tolerance induction to foreign antigens in old mice (24), the increased level ofT cells binding autologous erythrocytes in old mice (25) and men (26), and the increased response of old mice to chemically altered syngeneic erythrocytes (27) underlie an enhanced propensity to lose self-tolerance during senescence. Age-dependent changes in the capacity to maintain self-tolerance have also been suggested by the higher efficiency of polyclonal activators, such as lipopolysaccharide, to stimulate an autoantibody response against syngeneic erythrocytes in old mice. Because poly...

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contrasting

confidence: 54%

contrasting

confidence: 54%

Immunoregulation in senescence: increased inducibility of antigen-specific suppressor T cells and loss of cell sensitivity to immunosuppression in aging mice.

Doria¹,

Mancini²,

Adorini³

1982

Proc. Natl. Acad. Sci. U.S.A.

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“…calcium) of phagocytosis, considering the pervasive belief that phagocytic ingestion is a consequence of a mechanism similar to the excitation-contraction coupling which occurs in muscle (Silverstein et al, 1977). Hallgren et al (1978) (1980) and Uher et al (1981) found that magnesium could not substitute for calcium. Stossel (1973) found that calcium increased the rate of uptake of bovine serum albumin-coated paraffin oil particles by leukocytes, while Ito et al (1981) found that calcium was essential for the attachment of this same particle-type to peritoneal macrophages, but not for particle ingestion.…”

Section: Factors Regulating Phagocytosismentioning

confidence: 99%

Endocytosis: a review of mechanisms and plasma membrane dynamics

Besterman¹,

Low²

1983

Biochemical Journal

188

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“…Immune senescence appears to contribute to the increased susceptibility of the elderly to infectious diseases, to the decreased cell-mediated immunity, and to the limited effectiveness of immunization in this population (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28). There is general agreement that influenza vaccine efficacy is lower in elderly as compared to younger individuals (27)(28)(29).…”

mentioning

confidence: 99%

The Relationship Between Influenza Vaccine-Induced Specific Antibody Responses and Vaccine-Induced Nonspecific Autoantibody Responses in Healthy Older Women

Huang

Gauthey²,

Michel

et al. 1992

Journal of Gerontology

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The effect of aging on human humoral immunity was investigated by studying in vivo the relationship between influenza specific antibody responses and nonspecific vaccine-induced autoantibody responses in 32 independent, well-nourished older women volunteers (mean age 86 yr, range 74-97) and 23 young women volunteers (mean age 34 yr, range 23-46). Anti-influenza AITaiwanlll86(HlNl) antibody liters were determined by a hemagglutination inhibition test (Hi-test), and serum anti-dsDNA antibodies were measured by ELISA prior to, 15, and 30 days after influenza vaccination. The mean postvaccination fold increase (FI) of the anti-influenza antibody response was significantly lower in elderly individuals as compared to younger individuals. In contrast, the mean anti-dsDNA autoantibody level measured 30 days after vaccination was significantly increased in older volunteers as compared to younger ones. There was a significant negative correlation between the level of the FI of the anti-influenza antibodyresponse and the anti-dsDNA antibody response (r = -.441, p < .01). Our results suggest that the altered influenza specific antibody response was associated with an age-related increase in autoimmunity in aging individuals.

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Lymphocyte subsets and integrated immune function in aging humans

Cited by 76 publications

References 16 publications

Immunoregulation in senescence: increased inducibility of antigen-specific suppressor T cells and loss of cell sensitivity to immunosuppression in aging mice.

Immunoregulation in senescence: increased inducibility of antigen-specific suppressor T cells and loss of cell sensitivity to immunosuppression in aging mice.

Endocytosis: a review of mechanisms and plasma membrane dynamics

The Relationship Between Influenza Vaccine-Induced Specific Antibody Responses and Vaccine-Induced Nonspecific Autoantibody Responses in Healthy Older Women

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