Age-associated thymic atrophy is not associated with a deficiency in the CD44(+)CD25(-)CD3(-)CD4(-)CD8(-) thymocyte population.
Age-associated thymic atrophy has been proposed to be due to changes in both the thymic microenvironment and in the intrinsic properties of the early T cell progenitors, the CD44(+)CD25(-)CD3(-)CD4(-)CD8(-) cells. We have purified these cells from the thymus of both old and young mice and demonstrate no age-associated defect in their ability to differentiate into their progeny in vitro when used to reconstitute fetal thymic organ cultures. We also demonstrate that in the presence of anti-IL-7, CD44(+)CD25(-)CD3(-)CD4(-)CD8(-) cells from young mice show reduced thymocyte development in fetal thymic organ cultures compared with controls. Finally we have shown that old mice treated with IL-7 show improved thymopoiesis compared with control groups. The increased thymopoiesis seen in the old animals occurs in the sequential manner which would be anticipated for an agent working directly on the early stages, including the CD44(+)CD25(-)CD3(-)CD4(-)CD8(-) cells.
Aspinall
R
R
Department of Immunology, Faculty of Medicine, Imperial College of Science, Technology and Medicine, Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 9NH, United Kingdom.
Andrew
D
D
D000375:Aging / Q000276:immunology*; D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis*; D001284:Atrophy; D001853:Bone Marrow / Q000254:growth & development; D001854:Bone Marrow Cells / Q000166:cytology; D017252:CD3 Complex / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement; D003849:Deoxyguanosine / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D018960:Hyaluronan Receptors / Q000032:analysis*; D007153:Immunologic Deficiency Syndromes / Q000517:prevention & control; D015851:Interleukin-7 / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009924:Organ Culture Techniques; D011247:Pregnancy; D015375:Receptors, Interleukin-2 / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000166:cytology* / Q000187:drug effects; D013950:Thymus Gland / Q000196:embryology / Q000254:growth & development* / Q000276:immunology / Q000473:pathology
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D018960:Hyaluronan Receptors; D015851:Interleukin-7; D015375:Receptors, Interleukin-2; D003849:Deoxyguanosine