Abrogation of lymphocyte blastogenesis by a feline leukaemia virus protein

THYMIC atrophy and suppression of cell-mediated immunity (CMI) have been associated with feline leukaemia virus (FeLV) infection in cats1–5. Impairment of CMI by FeLV and other oncogenic retroviruses has been attributed to impaired lymphoid function caused by viral infection of lymphoid tissues5,6. This explanation for FeLV-related immunosuppression is plausible as lymphoid cells are the targets for oncogenesis3,7and atrophy of the thymus occurs early in the course of FeLV infection1,3,4. However, FeLV-associated immunological impairment is not due simply to viral destruction of the thymus as surgical thymectomy of kittens does not result in demonstrable immunosuppression8. Moreover, several observations indicate that the depressed CMI response of preleukaemic FeLV-infected cats may be due to T-cell unresponsiveness rather than T-cell deficiency: the circulating T-cell population is not decreased during the preleukaemic stage of the FeLV infection2; lymphocytes from FeLV-infected cats are unresponsive to phytomitogen-induced lymphocyte blastogenesis (LBT)2; and inhibition of the LBT response of normal feline lymphocytes can be produced by serum from FeLV-infected cats9. We have found that the unresponsiveness of feline lymphocytes to concanavalin A(Con A) also can be induced with FeLV inactivated by ultraviolet light10. Similar depressed mitogenic responses have been reported for mouse lymphocytes incubated with disrupted murine leukaemia virus11. Here we report that the mediator of FeLV-associated lymphocyte unresponsiveness seems to be the 15,000 molecular weight virion protein (p15) of FeLV.