Interleukin-10 production by splenic CD4+ cells and cell subsets from young and old mice.
We have examined whether aging is accompanied by changes in the capacity of CD4+ cells to produce IL-10, a potent immunoregulatory cytokine. Splenic CD4+ cells from young-adult and old C57BL/6NNia mice were stimulated in vitro with immobilized anti-CD3 epsilon mAb and were monitored for the release of IL-10 in short-term (3-day) cultures. In both age groups, detectable IL-10 accumulation in culture supernatants was stimulation dependent and reached a maximum level on Day 3. However, the peak IL-10 level in the old group was approximately 10-fold higher than that in the young-adult group. This age-associated difference in IL-10 production was also evident in the analysis of IL-10 mRNA levels in stimulated CD4+ cells. In contrast to these findings, the analysis of S-phase activity in the stimulated cell cultures revealed an age-related decline in this aspect of the cellular response. In studies on CD4+CD44lo and CD4+CD44hi subsets isolated from mice of various ages, we found that measurable IL-10 production segregated entirely with the CD44hi population, regardless of donor age. Taken together, our data suggest that the capacity for IL-10 synthesis by the splenic CD4+ cell pool is increased with age, and that the age-related shift toward a predominance of CD4+CD44hi cells in the peripheral tissues accounts for this quantitative change in IL-10 gene expression.
Hobbs
M V
MV
Department of Immunology, Scripps Research Institute, La Jolla, California 92037.
Weigle
W O
WO
Ernst
D N
DN
D000375:Aging; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D002352:Carrier Proteins / Q000032:analysis; D002478:Cells, Cultured; D018960:Hyaluronan Receptors; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface / Q000032:analysis; D016201:Receptors, Lymphocyte Homing / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000378:metabolism*
D002352:Carrier Proteins; D018960:Hyaluronan Receptors; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D016201:Receptors, Lymphocyte Homing; D016753:Interleukin-10