title: Induction of CD4+ regulatory T cells by TPA in mice: contra-suppression by CD8+ T cells.
abstract: Among the eight inbred mouse strains employed in our preceding report, 12-O-tetradecanoylphorbol 13-acetate (TPA) painting alone induced CD4+ regulatory T (Tr) cells in four strains (e.g., C3H/He) at 6-8 weeks of age, but not in the remaining strains (e.g., C57BL/6, BALB/c). In the present study, the effect of growth from 4-14 weeks on delayed-type hypersensitivity (DTH) response was investigated in three inbred murine strains, C3H/He (H-2k), C57BL/6 (H-2b) and BALB/c (H-2d) mice. In all strains older than 10 weeks, DTH response was suppressed exclusively by TPA painting. The defect of suppressive activity for DTH in several of the strains at 6-8 weeks of age was dependent on the presence of cells, which blocked regulatory cell activity at 6-8 weeks of age, but not at 10 weeks of age. The age-dependent difference in regulatory activity was caused by the presence of CD8+ contra-regulatory T (Tcr) cells. CD8+ contra-regulatory T cells are required to contact regulatory cells in order to block DTH suppressive activity. Adhesion molecules were of great importance in contra-suppression, as antibody treatment to LFA-1 or ICAM-1 blocked this activity. ICAM-1 expression on CD4 T cells greatly increased following growth in 10 week-BALB/c mice receiving TPA than 6-week-old mice, however, a slight increase in growth occurred in 6-to-10-week-old animals in which TPA was absent. The degree of increment in body weight was very similar in these inbred strains. Thymus involution in C3H/He mice was the earliest signal among these mice. This result may suggest that the period of differentiation and maturation of T cells in a first lymphoid tissue for the growth process differs in these three inbred strains. This study provides an interesting example of genetic control of maturation or proliferation of peripheral T cells.
authors.affiliation: Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Teikyo University, Tsukui-gun, Kanagawa, Japan. tanego@pharm.showa-u.ac.jp
authors.forename: Takaharu
authors.initials: T
authors.lastname: Negoro
authors.forename: Kazue
authors.initials: K
authors.lastname: Satoh
authors.forename: Fumio
authors.initials: F
authors.lastname: Iinuma
authors.forename: Takashi
authors.initials: T
authors.lastname: Tobe
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D001835:Body Weight; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D006968:Hypersensitivity, Delayed / Q000517:prevention & control; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D016169:Lymphocyte Function-Associated Antigen-1 / Q000032:analysis / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009929:Organ Size; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
chemical_list: D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1; D013755:Tetradecanoylphorbol Acetate