Failure of rearranged TCR transgenes to prevent age-associated thymic involution.
After puberty, the thymus undergoes a dramatic loss in volume, in weight and in the number of thymocytes, a phenomenon termed age-associated thymic involution. Recently, it was reported that age-associated thymic involution did not occur in mice expressing a rearranged transgenic (Tg) TCRalphabeta receptor. This finding implied that an age-associated defect in TCR rearrangement was the major, if not the only, cause for thymic involution. Here, we examined thymic involution in three other widely used MHC class I-restricted TCRalphabeta Tg mouse strains and compared it with that in non-Tg mice. In all three TCRalphabeta Tg strains, as in control mice, thymocyte numbers were reduced by approximately 90% between 2 and 24 mo of age. The presence or absence of the selecting MHC molecules did not alter this age-associated cell loss. Our results indicate that the expression of a rearranged TCR alone cannot, by itself, prevent thymic involution. Consequently, other presently unknown factors must also contribute to this phenomenon.
Lacorazza
H D
HD
Laboratory of T Cell Development, Immunology Program, Memorial Sloan-Kettering Cancer Center, New York 10021, USA.
Guevara Patiño
J A
JA
Weksler
M E
ME
Radu
D
D
Nikolić-Zugić
J
J
D000375:Aging / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D000818:Animals; D005260:Female; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor / Q000502:physiology*; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor / Q000502:physiology*; D016130:Immunophenotyping; D018655:Lymphocyte Count; D008285:Major Histocompatibility Complex / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D019076:Transgenes / Q000276:immunology* / Q000502:physiology
D016693:Receptors, Antigen, T-Cell, alpha-beta