Age-associated reshaping of the thymocyte differentiation model in male rats

Abstract

In order to elucidate the features of putative age-related changes in the intrathymic T cell maturation sequence, the thymus weight, thymocyte yield and relative proportions of thymocyte subsets were analyzed at distinct maturational stages (delineated by analysis of the expression of CD4/CD8 coreceptor molecules and TCR molecular complex) in male AO rats, from the peripubertal period (1 month of age) until 10 months of age. In 2-month-old rats both the thymus weight and lymphoid content were greater than in 1-month-old rats. The values of both parameters in 4-month-old rats were reduced to the corresponding values in 1-month-old rats. These levels were sustained until 10 months of age. However, the thymocyte composition was subjected to substantial changes during the whole period studied, probably due to alterations in action of both extrinsic and intrinsic factors which influence the ability of the thymus to support T cell maturation and/or feedback regulatory action of intrathymic CD4+ T cells on thymocytopoiesis (between the age of 7 and 10 months).

U cilju definisanja karakteristika procesa sazrevanja T ćelija u timusu u funkciji uzrasta, u mužjaka pacova AO soja, različitog uzrasta (od 1 meseca do 10 meseci) posmatrane su: težina timusa, ukupan broj timocita, kao i relativna zastupljenost pojedinih timocitnih subpopulacija (koje su razdvojene na osnovu ekspresije CD4/8 koreceptornih molekula i antigena TCRαβ molekulskog kompleksa). U životinja uzrasta 2 meseca i težina timusa i ukupan broj timocita bili su značajno veći nego u životinja uzrasta od mesec dana. Međutim, u životinja uzrasta od 4 meseca vrednost ovih parametra nije se razlikovala od vrednosti odgovarajućih parametara sa mesec dana. Vrednosti oba ova parametra nisu se bitno menjale od 4. do 10. meseca života. Sa druge strane, naši rezultati su pokazali značajne promene u relativnom odnosu timocitnih subpopulacija u ispitivanom periodu. Ove promene se mogu objasniti promenama u delovanju, kako spoljašnjih tako i unutrašnjih, faktora koji modulišu sposobnost timusne mikrosredine da podrži proces sazrevanja T ćelija i/ili utiču na efikasnost regulatornog delovanja intratimusnih CD4+ T ćelija, mehanizmom negativne povratne sprege, na proces sazrevanja T ćelija u timusu.