L asparaginase and alteration of lymphocyte surface: inhibition of the rat mixed leukocyte interaction

L Asparaginase has been shown to inhibit both cellular and humoral immune responses. This study dealt with the effects of the enzyme on lymphocytes' surface leading to inhibition of the one way rat mixed lymphocyte interaction in vitro. The animals employed were inbred strains of rats, Fischer, BN, BH, DA and their F₁ hybrids. Leucocyte cultures were prepared by dextran sedimentation of whole blood, conducted in triplicates and grouped as follows: untreated unmixed cells; untreated mixed cells; L asparaginase pretreated parental and untreated F₁ cells; enzyme pretreated F₁ and untreated parental cells, and pretreated F₁ and parental cells. Enzymatic treatment consisted of 90 min incubation of 1 x 10⁶ lymphocytes with 20 IU L asparaginase which was then washed off. All cultures were incubated at 37°C, 5% CO₂, for 3-9 days when their DNA synthesis was assayed by TdR ³H incorporation. The data demonstrated that a short pretreatment with the enzyme of either parental or F₁ hybrid rat lymphocytes temporarily inhibited their proliferative response as measured by their DNA synthesis which lagged 24 hr behind the untreated mixed control populations. L Asparaginase may alter the surface of lymphocytes directly or indirectly leading to interference with binding and recognition of antigen, mitogen, or transplantation antigens. Any such interference with the initial events of the immune response may account for its immunosuppressive activity.