Aged mice exhibit in vivo defective peripheral clonal deletion of D(b)/H-Y reactive CD8(+) T cells.
We previously reported that T cells from aged mice were resistant to activation-induced cell death (AICD) in vitro. To determine whether the presence of AICD-resistant T cells is associated with defects in age-related peripheral clonal deletion in vivo, congenic male SCID mice were reconstituted with T cells from aged or young female D(b)/H-Y TCR (Tg71) transgenic mice. Compared with recipients of young cells, the recipients of T cells from aged mice exhibited a 3-fold increase in the percentage of autoreactive CD8(+) H-Y antigen-reactive T cells as defined by the clonotypic antibody, M33. There were significantly increased sera levels of interferon-gamma, a significantly decreased expression of FasL by M33(+)CD8(+) T cells, and significantly decreased apoptosis by DNA fragmentation staining of the spleen of mice reconstituted with T cells from aged mice compared to those from young mice. By day 21, the recipients of T cells from aged mice but not young mice, exhibited infiltration of CD3(+) cells into the non-lymphoid organs. These results indicate that there is defective peripheral deletion of the self-reactive T cells derived from aged female Tg71 mice, and that failure to delete these cells is associated with the defective T-cell clonal deletion in the recipient mice.
Hsu
H C
HC
Division of Clinical Immunology and Rheumatology, Department of Medicine, The University of Alabama at Birmingham, 701 South 19th Street, LHRB 473, Birmingham, AL 35294-0007, USA.
Zhou
T
T
Shi
J
J
Yang
P A
PA
Liu
D
D
Zhang
H G
HG
Bluethmann
H
H
Mountz
J D
JD
D019264:Adoptive Transfer; D000375:Aging / Q000276:immunology*; D000818:Animals; D017209:Apoptosis; D017252:CD3 Complex; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D053222:Fas Ligand Protein; D005260:Female; D006183:H-2 Antigens / Q000276:immunology*; D006182:H-Y Antigen / Q000276:immunology*; D064532:Histocompatibility Antigen H-2D; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D007668:Kidney / Q000166:cytology; D008099:Liver / Q000166:cytology; D008168:Lung / Q000166:cytology; D008198:Lymph Nodes; D008285:Major Histocompatibility Complex / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D010641:Phenotype; D013154:Spleen
D017252:CD3 Complex; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D006183:H-2 Antigens; D006182:H-Y Antigen; D064532:Histocompatibility Antigen H-2D; D018960:Hyaluronan Receptors; D008562:Membrane Glycoproteins; D007371:Interferon-gamma