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

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.