Age-dependent loss of naïve T cells in TCR transgenic bone marrow chimeras.
Study of immune senescence is complicated by low numbers of antigen-specific lymphocytes, particularly naïve T (Tn)cells which disappear with aging. Although T cell receptor (TCR) transgenic mice facilitate aging research, their large number of Ag-specific T cells renders their T cell pool abnormal, precluding normal in vivo immunity. To create a physiologically relevant model with measurable numbers of TCR transgenic CD4+ T cells in the context of normal lymphocytes, mixed (DO11.10+BALB/c) bone marrow (BM) chimeras were constructed. As found in normal mice, the total number of transgenic T cells and the Tn:memory T cell ratio declined with the aging of the BM chimeras. Although these shifts in T cell subsets were evident in both the lymph nodes and the spleen (SP), they were more pronounced in the SP. Unlike DO11.10 mice, transgenic T cells in the chimera acquired an effector/memory phenotype upon antigen challenge. These results reveal a pliable model to study the impact of the constriction of the Tn cell repertoire upon optimal vaccine responses in the elderly.
Coleman
Clenton
C
Department of Biology, Rider University, 2083 Lawrenceville Road, Lawrenceville, NJ 08648-3099, USA.
Howell
Koko
K
Hobbs
Monte V
MV
Riggs
James E
JE
D019264:Adoptive Transfer; D000375:Aging / Q000276:immunology*; D000818:Animals; D001853:Bone Marrow / Q000276:immunology; D016026:Bone Marrow Transplantation; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D013154:Spleen / Q000166:cytology / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018183:Transplantation Chimera / Q000276:immunology*