Reduced primary T lymphopoiesis in 3-month-old lurcher mice: sign of premature ageing of thymus?
OBJECTIVE
The nervous, endocrine and immune systems are functionally interconnected so that they may form a complex metasystem. Abnormalities within the neuroendocrine compartment can thus affect immune mechanisms and vice versa. The Lurcher-type mutation in mice has a profound impact on brain development in both homozygous and heterozygous individuals, which is followed by immune system changes. We investigated whether macroscopic changes in the thymus size were associated with an altered thymocyte development or with changes in peripheral T cell subset distribution.


METHODS
CD3, CD4 and CD8 expressions on thymocytes and peripheral T cells were compared with those in wild-type and Lurcher heterozygous C3H mice using surface immunophenotyping and flow cytometry. Galanthus nivalis agglutinin binding to thymocytes was measured at the same time.


RESULTS
While no differences between experimental groups were observed in 1-month-old mice, a critical reduction of numbers of thymocytes and namely double-positive cells occurred before the age of 3 months in Lurcher mice, which was accompanied by thymus involution. Interestingly, this was not accompanied by significant differences in major T subset proportions in the peripheral lymphatic tissue.


CONCLUSIONS
We interpret our observations as hallmarks of premature thymus ageing in heterozygous Lurcher mice with only a marginal effect in the periphery in early adulthood.
Department of Pathology and Molecular Medicine, Charles University, 2nd Medical Faculty and University Hospital Motol, Prague, Czech Republic. p.mandak@email.cz
Petra
P
Mandakova
Jiri
J
Sinkora
Petr
P
Sima
Frantisek
F
Vozeh
D000375:Aging; D000818:Animals; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism; D015704:CD4 Antigens / Q000276:immunology / Q000378:metabolism; D016827:CD8 Antigens / Q000276:immunology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D007150:Immunohistochemistry; D038041:Lymphopoiesis; D051379:Mice; D008818:Mice, Neurologic Mutants; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology / Q000473:pathology
D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens