Elsevier

Cellular Immunology

Volume 139, Issue 2, February 1992, Pages 426-437
Cellular Immunology

Splenic and inguinal lymph node T cells of aged mice respond differently to polyclonal and antigen-specific stimuli

https://doi.org/10.1016/0008-8749(92)90083-2Get rights and content

Abstract

Numerous changes have been reported to occur in T cell responsiveness of mice with increasing age. However, most of these studies have examined polyclonal stimulation of spleen cells from a limited number of mouse strains. This study investigated the influence of genetic background, source of lymphocytes, and type of stimulus on age-associated changes in T cells response. Con A-induced proliferation and IL-2 and IFN-γ production by splenic lymphocytes (SL) was significantly greater in CBA/Ca mice compared to C57BL/6 mice, regardless of age. SL of both strains exhibited the predicted age-dependent decline in proliferative response and an increase in IFN-γ production in response to Con A. In contrast, however, only SL from C57BL/6 mice demonstrated the predicted age-dependent decline in Con A-induced IL-2 production; Con A-induced SL of young and aged CBA/Ca mice produced comparable amounts of IL-2. Differences in age-associated responses to Con A were also observed between SL and inguinal lymph node (ILN) cells of CBA/Ca mice. In contrast to SL, ILN cells demonstrated an increased proliferative response to Con A. However, lymphokine production by Con A-stimulated ILN cells from aged CBA/Ca mice was similar to that of Con A-stimulated SL from aged CBA/Ca mice. To determine if aged ILN T cells respond similarly to polyclonal and antigen-specific stimuli, keyhole limpet hemocyanin (KLH) responses of T cells isolated from ILN of aged and young CBA/Ca mice were examined. KLH-specific T cells from aged mice cultured with KLH-pulsed macrophages (Mφ) from aged mice were significantly reduced in their ability to proliferate compared to KLH-specific T cells of young mice cultured with young KLH-pulsed Mφ. In contrast to the expected results, the defect was not at the level of the T cells; proliferation of young T cells cultured with aged KLH-pulsed Mφ was equivalent to the proliferation of aged T cells cultured with aged Mφ. These results suggest that aging has differential effects on polyclonal and antigen-specific T cell proliferation and on polyclonal stimulation of T cells isolated from different lymphoid organs and from different Strains of mice.

References (22)

  • L.N. McKernan et al.

    Cell. Immunol

    (1988)
  • D.A. Kirschmann et al.

    Cell. Immunol

    (1991)
  • T. Makinodan et al.
  • D. Zharhary et al.

    Mech. Ageing Dev

    (1984)
  • C.S. Vissinga et al.

    Cell. Immunol

    (1987)
  • T.C. Fong et al.

    Cell. Immunol

    (1989)
  • M. Bruley-Rosset et al.

    Mech. Ageing Dev

    (1984)
  • E.H. Perkins et al.

    Mech. Ageing Dev

    (1983)
  • D.M. Murasko et al.

    Exp. Gerontol

    (1991)
  • K.J. Blank et al.

    J. Interferon Res

    (1985)
  • D.M. Murasko et al.

    Annu. Rev. Gerontol. Geriatr

    (1990)
  • Cited by (61)

    • Sex as a confounding factor in the effects of ageing on rat lymph node t cell compartment

      2020, Experimental Gerontology
      Citation Excerpt :

      In LNs and PB from rats of both sexes, the CD4+/CD8+ T cell ratio decreased with age, but to a greater extent in males. Similar changes were found in murine SLOs (Kirschmann and Murasko, 1992; Arsenović-Ranin et al., 2017) and human blood (Ferguson et al., 1995). Of note, the ageing-related decline in this ratio in humans is considered to be not only a surrogate biomarker of immunosenescence, but also an independent predictor of all-cause mortality (Ferguson et al., 1995).

    • Strain specificities in influence of ageing on germinal centre reaction to inactivated influenza virus antigens in mice: Sex-based differences

      2020, Experimental Gerontology
      Citation Excerpt :

      This decline in the number of GC B splenocytes correlated with the age-associated decrease in B-cell activation/proliferation in response to TIV in splenocyte cultures, as shown by Ki-67 staining. This age-related decrease in B-cell activation/proliferation could reflect not only the B cell intrinsic changes occurring with ageing (Frasca et al., 2003), but also, as previously suggested (Kirschmann and Murasko, 1992; Swain et al., 2005), the decline in the capacity of CD4+ T cells to proliferate in response to antigenic stimulation (as shown in TIV-restimulated splenocyte cultures) and thereby to provide optimal help to the B cells. Additionally, the age-related decrease in B cell proliferation may reflect downregulation of CD154 (CD40L), the key molecule providing direct CD4+ T cell-to-B cell communication, due to chronic energy stress in CD4+ T cells occurring with ageing (Eaton et al., 2004; Weyand and Goronzy, 2016; Yu et al., 2012).

    • Strain specificities in age-related changes in mechanisms promoting and controlling rat spinal cord damage in experimental autoimmune encephalomyelitis

      2018, Experimental Gerontology
      Citation Excerpt :

      This could reflect the greater frequency of MBP responsive cells in dLNs of aged AO rats, and consequently in dLN cell cultures at the beginning of the restimulation, and/or their greater proliferative response to MBP stimulation. In accordance with some previous studies (Kirschmann and Murasko, 1992; Nikolich-Zugich et al., 2012), the analyses of proliferation of freshly isolated and ConA-stimulated CD8+ T lymphocytes in dLN cell cultures showed age-related decline in their proliferation capacity, which was especially prominent in AO rats. Strain specificities in T lymphocytes proliferation to mitogen (Sydney et al., 2014) and, particularly important, in the age-related changes in their proliferative capacity (Kirschmann and Murasko, 1992) have already been shown.

    • Strain specificities in cellular and molecular immunopathogenic mechanisms underlying development of experimental autoimmune encephalomyelitis in aged rats

      2017, Mechanisms of Ageing and Development
      Citation Excerpt :

      Given that the activated CD4+ T lymphocytes are the main producers of IL-2 (Nelson, 2004), it is highly likely that its production was greater in CD4+ lymphocytes from AO rat dLN cell cultures. The discrepancy between hereby reported findings and those previously obtained in dLN cell cultures from strain-matched young rats (Stojić-Vukanić et al., 2016; Vukmanović et al., 1989), could be reconciled by data indicating that in mice, aging influences CD4+ lymphocyte IL-2 production in a strain-specific manner (Kirschmann and Murasko, 1992; Kubo and Cinader, 1990). To further support the previous notion are data indicating that aging does not affect IL-2 production by CD4+ T lymphocytes from Fischer 344 rats in culture (Holbrook et al., 1989).

    View all citing articles on Scopus

    Supported by NIH AG08659.

    View full text