Long‐term T‐cell‐mediated immunity to epstein‐barr virus in man. IV. Development of T‐cell memory in convalescent infectious mononucleosis patients

Abstract

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.

Active lytic infection of human primary tonsillar B cells by KSHV and its noncytolytic control by activated CD4+ T cells

“…In the EBV field, it has long been known that, in seropositive individuals, the outgrowth of EBV-immortalized lymphoblastoid cell lines from primary lymphoid cultures is facilitated by either T cell depletion or treatment with CsA (29)(30)(31)(32). However, mechanistically that process is completely different: it is a result of an adaptive immune response that (a) requires specific anti-viral CD8 + T cells, (b) is mediated by killing of the EBV-infected target cell, (c) is MHC class I restricted, and (d) is primarily directed against latently infected cells (not lytically infected cells) (33)(34)(35)(36)(37). In contrast, the process we describe here is not dependent upon virus-specific adaptive immunity.…”

Epstein-Barr virus transformation: involvement of latent membrane protein 1-mediated activation of NF-κB

“…When delayed until adolescence or adulthood, primary EBV infection can cause infectious mononucleosis (Henle et al, 1968). Although the primary infection is controlled principally by an antiviral T-cell response, EBV persists for the lifetime of the individual by infecting and establishing a latent infection in memory B lymphocytes (Babcock et al, 1998;Nilsson et al, 1971;Rickinson et al, 1975Rickinson et al, , 1980Yao et al, 1989). B lymphocytes latently infected with EBV have the potential to produce inde®nitely proliferating lymphocytes as evidenced by the outgrowth of EBV-transformed lymphoblastoid cell lines (LCLs) when peripheral blood B lymphocytes are cultured in vitro (Henle et al, 1967).…”

HLA antigen-related restriction of T lymphocyte cytotoxicity to Epstein-Barr virus.

“…It should be emphasized, however, that although EB virus-specific memory T cells have been readily demonstrated in normal seropositive donors, they have not been detected in IM patients until at least 5-23 weeks after onset (17). Clearly, the effector mechanisms operating during the early stages of IM may be'separate from those involved in later specific memory function.…”