Perturbation of the T cell receptor repertoire occurs with increasing age in dogs. (February 2018) - Holder, Angela
Abstract: Immunosenescence is the gradual deterioration in immune system function associated with ageing. This decline is partly due to involution of the thymus, which leads to a reduction in the output of naive T cells into the circulating lymphocyte pool. Expansion of existing naive and memory T cell populations, to compensate for the reduction in thymic output, can lead to reduced diversity in the T cell repertoire with increasing age, resulting in impairment of immune responses to novel antigenic challenges, such as during infection and vaccination. Since associations between T cell repertoire and age have only been examined in a limited number of species, to gain further insights into this relationship, we have investigated age-related changes in the canine T cell receptor (TCR) repertoire. Blood samples were obtained from Labrador retriever dogs of varying ages and variation in the complementary determining region 3 (CDR3) of the T cell receptor beta (TCRB) chain was investigated. CDR3 size spectratyping was employed to evaluate clonal expansion/deletion in the T cell repertoire, allowing identification of profiles within individual variable (V) region families that skewed away from a Gaussian distribution. Older dogs (10–13 years) were found to have an increased number of TCRB V gene spectratypes that demonstrated a skewed distribution, compared with young dogs (≤3 years). Additionally, there was a reduction in the number of clonal peaks present in the spectratypes of old dogs, compared with those of young dogs. The study findings suggest that there is an age-associated disturbance in the diversity of the T cell receptor repertoire in dogs. Highlights: The diversity of the human T cell repertoire is known to reduce in old age. Canine T cell receptor repertoire diversity was analysed using CDR3 spectratyping. An age-associated disturbance was identified in the T cell repertoire of dogs.