Defects of immune cells in the senescence-accelerated mouse: a model for learning and memory deficits in the aged.
We investigated immune characteristics of SAMP8 mice that have early learning and memory deficiencies and a short life span accompanied by normal growth and compared them to those of SAMR1 mice that have a normal aging process. The indexes of immune responsiveness used were natural killer (NK) cell activity, in vitro anti-SRBC (sheep red blood cells) antibody responses, cell proliferation, and interleukin 2 (IL-2)-producing activity in response to concanavalin A of spleen cells. As early as 2 months after birth, SAMP8 mice showed markedly low activity for all the indexes that was not due to a delay of their development. Endogenous NK cell activity in SAMP8 mice remained low or at the background level for a few months, but the trace level of this activity increased after treatment with an immune potentiator of polyinosinic-polycytidylic acid. Because the number of cells bearing an NK cell marker in SAMP8 mice was comparable to that for SAMR1 mice, the low NK cell activity found for SAMP8 mice may not be caused by a low number of precursor cells but by defects in the lytic mechanism or low competence. Flow cytometry analyses showed that the size of the lymphocyte fraction in the spleen is the same for both strains and that T cell fractions, especially of CD4+ T cells in SAMP8 mice are smaller than in SAMR1 mice. In contrast, a B cell fraction was somewhat larger in SAMP8 mice. Together with the fact that the spleen cells of both strains equally stimulated allogeneic T cells in the mixed lymphocyte reaction, the low helper T cell activity in antibody responses, even under the condition of cell-number equivalence, indicates a qualitative defect of CD4+ T cells in SAMP8 mice. This defect probably is closely related to the low endogenous activity of NK cells.
Central Research Laboratories, Asahi Breweries, Ltd., Tokyo, Japan.
Y
Y
Abe
M
M
Yuasa
Y
Y
Kajiwara
M
M
Hosono
D000375:Aging / Q000276:immunology* / Q000523:psychology; D000818:Animals; D002455:Cell Division / Q000276:immunology; D002460:Cell Line; D003601:Cytotoxicity Tests, Immunologic; D004912:Erythrocytes / Q000276:immunology; D005434:Flow Cytometry; D006462:Hemolytic Plaque Technique; D007376:Interleukin-2 / Q000032:analysis; D007694:Killer Cells, Natural / Q000276:immunology*; D007858:Learning; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D011598:Psychoneuroimmunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012756:Sheep / Q000276:immunology; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D007376:Interleukin-2