The role of the thymus in the maintenance of natural killer cells in vivo

Abstract This report describes a model for investigating the role of the thymus in regulating natural killer (NK) cell activity in vivo . Evidence is presented that the thymus can regulate NK cells, and that at least some NK cells can develop without thymic help. Marrow from thymectomized rats depleted of circulating T cells by thoracic duct cannulation was transplanted into rats without a thymus (1 ° ATX.BM). These 1 ° ATX.BM rats had NK cell levels above controls 3 months after reconstitution but markedly depressed NK cell levels by 9 months. When 1 ° ATX.BM marrow was used to reconstitute rats with or without a thymus, those without a thymus (2 ° ATX.BM) exhibited low NK cell levels after 3 months, and a similar result was obtained when 2 ° ATX.BM marrow was used to reconstitute 3 ° ATX.BM rats. The low NK cell levels in 2 ° and 3 ° ATX.BM rats were due to a deficiency in spontaneously cytotoxic NK cells, as they had normal numbers of interferon-responsive pre-NK cells. Spleen cells from 2 ° and 3 ° ATX.BM rats produced less interferon than control spleen cells when cultured with P815 tumor cells in vitro . However, 2 ° and 3 ° ATX.BM rats had higher numbers of large granular lymphocytes than controls despite their low NK cell levels. In marked contrast to 2 ° and 3 ° ATX.BM rats, spleen cells from 4 ° ATX.BM rats had higher levels of cytotoxicity and a higher frequency of both spontaneously cytotoxic and pre-NK cells than controls. The 4 ° ATX.BM rats also had the highest frequency of large granular lymphocytes in the spleen.