Monday, 18 August 2014

Aging Rats have a different immune system

Djikić J, Nacka-Aleksić M, Pilipović I, Stojić-Vukanić Z, Bufan B, Kosec D, Dimitrijević M, Leposavić G. Age-associated changes in rat immune system: Lessons learned from experimental autoimmune encephalomyelitis. Exp Gerontol. 2014 Aug 13. pii: S0531-5565(14)00240-X. doi: 10.1016/j.exger.2014.08.005. [Epub ahead of print]

Aging is associated with the decline in immune response to infectious agents and tumors and increasing risk of autoimmunity, but the incidence of autoimmune diseases does not increase in the elderly. To elucidate the cellular and molecular mechanisms influencing clinical expression of autoimmunity in aged animals, the phenotypic and functional characteristics of mononuclear cells isolated from the spinal cords of 3-month-old (young) and 26-month-old (aged) Dark Agouti rats immunized to induce experimental autoimmune encephalomyelitis (EAE) - the model of multiple sclerosis, the most common autoimmune disease of the central nervous system, were examined. Aged rats were less susceptible to EAE induction, and the neurological and histological picture was milder in those rats which developed the clinically manifested disease. At the peak of the disease, several times fewer mononuclear cells and T lymphocytes were isolated from the spinal cords of aged rats compared with the young ones. The frequency of CD4+ cells among TCRαβ+ lymphocytes, as well as that of reactivated CD134(OX40)+ cells within its CD4+ T-lymphocyte subpopulation, was less in spinal cords of aged compared with young rats. Additionally, CD134 surface density on CD4+ lymphocytes was decreased in the spinal cord of aged rats. The changes in CD134 expression most likely reflected in part age-related intrinsic changes in CD4+ lymphocytes as the expression of this molecule was also impaired on in vitro stimulated naïve CD4+ splenocytes from aged rats compared with young animals. In addition, greater frequency of CD8+ lymphocytes with regulatory phenotypes could also contribute to impaired CD4+ cell reactivation in aged rats. The increased apoptosis of CD4+ cells from aged rats was consistent with their impaired reactivation and it was accompanied by the greater frequency of CD4+CD11b+CD45int/high cells, which are supposed to be actively engaged in apoptotic cell phagocytosis and to have immunoregulatory properties. Compared with young rats, following short-term PMA and ionomycin stimulation in vitro, the frequency of IL-17+ and IFN-γ+CD4+ T lymphocytes among the spinal cord mononuclear cells from aged rats and the cytokine expression density on a per lymphocyte basis were reduced. Additionally, the increase in the proportion of autoregulatory IL-17+IL-10+ on the account of proinflammatory IL-17+IFN-γ+ cells within IL-17+ lymphocytes suggested their lower pathogenic capacity in aged rats. This most likely reflected alterations in the aged rat spinal cord cytokine milieu, which were mirrored in a diminished expression of IL-1β mRNA followed by an enhanced expression of IL-6 and TGF-β mRNA. Overall, the study points to age-related changes in T lymphocytes and other cells from the spinal cord infiltrate which could contribute to the decreased susceptibility of aged rats to the induction of EAE.

In this study aged rats got less severe EAE and therefore not surprisingly there was fewer cells in the CNS of these animals, because the two elements are intimately associated therfore you would expect and got less inflammatory cytokines. In this study they argue for more active regulation. In relapsing EAE as animals get older their relapsing disease burns out,just as this does in human MS, but the important element with regard to aging is probably how we deal with the consequences of the attacks and as we or animals get older they deal with the consequences less well and are more likely to to go progressive. This occurs also in MS such that those people with longer disease duration and older onset are more likely to go progressive. Therefore the question is what are the youth factors that limit this activity. Maybe DoctorLove will be able to tell us, so watch this space 

No comments:

Post a Comment

Please note that all comments are moderated and any personal or marketing-related submissions will not be shown.