CD26/dipeptidyl peptidase 4-deficiency alters thymic emigration patterns and leukcocyte subsets in F344-rats age-dependently.
As CD26 (dipeptidyl peptidase 4/DPP4) rapidly truncates incretins N-terminally, including glucagon-like peptide-1, DPP4-inhibitors have been developed for treatment of diabetes type 2. To some extent this is surprising, as CD26/DPP4 is also deeply involved in immune regulation. Long-term pharmacological studies are hampered by off-target inhibition of DPP4-homologues. Therefore, we studied the effects of genetic CD26/DPP4-deficiency by investigating blood, spleen and thymus leucocyte subpopulations of wild-type and CD26-deficient F344-rats at different ages. In young animals at 1 and 3 months of age, there were no differences in leucocyte subsets, while in older animals the T cell composition was changed significantly. From the age of 6 months onwards, reduced numbers of recent thymic emigrants and memory T cells, and consequently an increased amount of naive T cells were observed in CD26-deficient rats. In addition, the architecture of the thymus was altered, as observed by a reduced density of lymphocytes in the medulla. Furthermore, the number of proliferating cells in the thymus was decreased in CD26-deficient rats at a higher age. Moreover, CD26-deficiency resulted in markedly reduced numbers of B cells in later life. Additionally, an age- but not CD26-dependent increase of regulatory T cells and a decrease of natural killer cell numbers were detected in the blood and spleen. Our findings indicate an important role of CD26 in maintaining lymphocyte composition, memory T cell generation and thymic emigration patterns during immunosenescence, with possible implications for using DPP4-inhibitors.
Klemann
C
C
Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany.
Schade
J
J
Pabst
R
R
Leitner
S
S
Stiller
J
J
von Hörsten
S
S
Stephan
M
M
D000375:Aging / Q000276:immunology* / Q000473:pathology; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D018819:Dipeptidyl Peptidase 4 / Q000172:deficiency*; D005260:Female; D005838:Genotype; D006098:Granulocytes / Q000276:immunology; D007156:Immunologic Memory; D007694:Killer Cells, Natural / Q000276:immunology; D007958:Leukocyte Count; D016131:Lymphocyte Subsets / Q000276:immunology*; D051381:Rats; D011916:Rats, Inbred F344; D016176:T-Lymphocyte Subsets / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology* / Q000473:pathology; D015430:Weight Gain / Q000276:immunology
D018819:Dipeptidyl Peptidase 4