Long-term T-cell-mediated immunity to Epstein-Barr virus in man. IV. Development of T-cell memory in convalescent infectious mononucleosis patients.

Under appropriate culture conditions, EB virus infection of lymphocytes from seropositive donors leads to regression of transformation, and this was shown previously to be due to activation in a secondary immune response to T lymphocytes inhibitory for the autologous lymphoblastoid cell line. Regression can be quantified by determining the number of cells required for its expression. To investigate the development of memory T cells with EB-virus specificity in the primary infection, a comparison was made of the capacity for regression of lymphocytes from 16 cases of infectious mononucleosis (IM) and 13 normal donors. With 9 normal seropositive donors a mean lymphocyte concentration of 4.6 X 10(5)/ml was required to achieve 50% regression. In contrast, with 8 cases of IM tested within 1 week of onset, a much higher mean lymphocyte concentration (3.7 X 10(6)/ml) was necessary. Six of these IM cases, and another not tested in the first week, were tested on several occasions between 5 and 23 weeks after onset, and showed a slight reduction in the mean cell concentration required for regression (1.5 X 10(6)/ml). Six additional were tested 23--83 weeks after onset by which time the cell concentration required for 50% regression (mean = 4.5 X 10(5)/ml) had reached the level shown by normal seropositive donors. Regression did not occur with lymphocytes from seronegative donors, even at the highest cell concentration. Recombination cultures of T-cell-depleted and T-cell-enriched lymphocyte populations from 3 IM cases in ratios of 1:7 to 7:1 showed that the failure of regression in acute IM was not due simply to lack of sufficient numbers of T cells. The results indicate that EB-virus-specific memory T-cell activity as detected by the regression test is absent in the acute phase of IM, becomes evident at low levels 5--23 weeks after onset, and reaches a maximum after about 6 months.