Recovery of T-cell functions in aged mice injected with synthetic thymosin-α1

Frasca, Daniela; Garavini, Mauro; Doria, Gino

doi:10.1016/0008-8749(82)90487-7

Cited by 43 publications

(9 citation statements)

References 24 publications

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“…Perhaps growth hormone, prolactin, or both acted directly on T lymphocytes to increase their ability to proliferate and secrete IL-2. All three of these possibilities are consistent with earlier findings in which T-cell-mediated immune events were restored in aged rats by syngeneic thymic grafts (5) or by treatment with either thymosin a, or IL-2 (6,7,26). Whatever the mechanism of action of GH3 cells, these data show that factors extrinsic to the immune system can reverse some components of the decline in T-cell-mediated immunity that occurs during aging.…”

Section: Resultssupporting

confidence: 91%

See 1 more Smart Citation

GH3 pituitary adenoma cells can reverse thymic aging in rats.

Kelley¹,

Brief²,

Westly³

et al. 1986

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

239

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Thymic size and T-cell function decrease with age, and it has not yet been possible to totally reverse this thymic atrophy and completely restore T-cell-dependent immune functions. In this study, GH3 pituitary adenoma cells, which secrete growth hormone and prolactin, were implanted subcutaneously into 16-and 22-month-old female Wistar-Furth rats and the rats were sacrificed approximately 2 months later. Only thymic remnants were detected in aged, non-implanted rats, but thymus glands were found in both the 18-and the 24-month-old rats that had been implanted with GH3 cells. Thymus glands from the GH3-implanted 18-month-old rats contained distinct cortical thymocytes and medullary epithelial cells. Depending on the concentration of phytohemagglutinin or concanavalin A, T-cell proliferative responses of splenocytes from these implanted rats were 2-to 5-fold greater than those of 18-month-old controls. At the optimal concentration of mitogen, proliferative responses to either lectin could be restored to those levels observed in splenocytes from 3-monthold Wistar-Furth females. Thymus glands from 24-month-old GH3-implanted rats contained more cortical thymocytes and fewer fat vacuoles than controls, but they were not totally reconstituted. No significant lectin-induced T-cell proliferative responses or IL-2 secretion were detected in 24-month-old control rats, but splenocytes from GH3-implanted rats showed augmented T-cell proliferative responses and increased synthesis of IL-2. Fluorescence-activated cell-sorter analysis of thymocytes revealed that 24-month-old rats implanted with GH3 cells had a higher proportion of lymphocytes with the Thy-1.1 and helper-T-cell phenotypes. These data show that it is possible to regenerate normal thymic tissue in situ and reverse the natural loss in cell-mediated immunity that occurs with aging.

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Section: Resultssupporting

confidence: 91%

“…Thymic atrophy precedes the decline in T-cell proliferation, and thymic implants or thymic hormones can partially restore the diminished T-cell proliferation that occurs during aging (5)(6)(7). For these and other reasons, it has been argued that the thymus gland is the clock for immunologic aging (2,8,9).…”

mentioning

confidence: 99%

GH3 pituitary adenoma cells can reverse thymic aging in rats.

Kelley¹,

Brief²,

Westly³

et al. 1986

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

239

View full text Add to dashboard Cite

show abstract

“…Most recently, we have developed a radioimmunoassay (RIA) for Tp4 [40] and have found that murine p4 levels also decline with age. Hirokawa et al [27] provided histo logical confirmation that the epithelial cells in the thymic medulla which contain Tai decline in the second decade, in parallel with the postpubertal thymic involution and de cline in serum T a1 levels, as measured by RIA [39,62], Evidence that this decrease in thymic hormone output is related to the agerelated decrease in immunological parame ters comes from multiple studies showing that synthetic Tai in vivo or in vitro repairs the deficient helper T cell response in aged mice and in man [13,14,16,17], Similarly, injection of FTS [2] and TP-1 [47] results in partial reversal of immunological deficien cies of aging. Weksler et al [63] have re ported that TP-5 is effective in vitro and in vivo in reversing the immunological effects of aging on generation of antibody plaque forming cells.…”

Section: Role Of Thymic Hormones In Agingmentioning

confidence: 99%

Thymosins, Lymphokines, and the Immunology of Aging

Zatz¹,

Goldstein²

1985

Gerontology

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Recent data point to a significant role for thymosins, lymphokines, and other soluble mediators in the senescence of the immune response that occurs with aging. In recent years, considerable progress has been made in the isolation and physiochemical characterization of several of these soluble mediators. We are now beginning to define the mechanisms by which these molecules regulate and mediate immune responses. In this paper we review the properties of the best characterized thymic hormones and lymphokines and focus on the role of the endocrine thymus in modulating immune responses. Of particular interest is the recent observation that thymosin fraction 5 can enhance production of interleukin-2 (IL-2) and colony-stimulating factor (CSF), and that IL-2 production, but not CSF production, is selectively diminished in aging mice. Several of the products of the immune system also can act as neuroactive immunotransmitters and modulate a number of neuroendocrine responses. Current studies point to an important role for these molecules in modulating neuroendocrine function, suggesting a broader role for the endocrine thymus in the aging process.

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“…One function of the thymus thought to be important in T cell differentiation is the production of thymic hormones 45 . Injection of purified thymic hormones, including thymosin, thymopoietin, and thymulin, into aged animals and humans does somewhat improve several parameters of immune function, including the activity of antigen‐specific helper T cells, the generation of specific antibody responses, and alloreactive cytolytic cells 46–50 …”

Section: Effect Of Interleukin‐2 On In Vitro Responses Of Young Adumentioning

confidence: 99%

Role of Interleukin‐2 in the Age‐Related Impairment of Immune Function

Thoman

1985

J American Geriatrics Society

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Recovery of T-cell functions in aged mice injected with synthetic thymosin-α1

Cited by 43 publications

References 24 publications

GH3 pituitary adenoma cells can reverse thymic aging in rats.

GH3 pituitary adenoma cells can reverse thymic aging in rats.

Thymosins, Lymphokines, and the Immunology of Aging

Role of Interleukin‐2 in the Age‐Related Impairment of Immune Function

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