CD4 T cells are important for control of infection with murine gammaherpesvirus 68 (␥HV68),
Strategies to prime CD8؉ T cells against Murine gammaherpesvirus 68 (␥HV68; MHV68) latency have, to date, resulted in only limited effects. While early forms of latency (<21 days) were significantly reduced, effects were not seen at later times, indicating loss of control by the primed CD8 ؉ T cells. In the present study, we evaluated CD8؉ T cells in an optimized system, consisting of OTI T-cell-receptor (TCR) transgenic mice, which generate clonal CD8 ؉ T cells specific for K b -SIINFEKL of OVA, and a recombinant ␥HV68 that expresses OVA (␥HV68.OVA). Our aim was to test whether this optimized system would result in more effective control not only of acute infection but also of later forms of latent infection than was seen with previous strategies. First, we show that OTI CD8 ؉ T cells effectively controlled acute replication of ␥HV68.OVA in liver, lung, and spleen at 8 and 16 days after infection of OTI/RAG mice, which lack expression of B and CD4 ؉ T cells. However, we found that, despite eliminating detectable acute replication, the OTI CD8 Infection of immunocompetent mice with gammaherpesvirus 68 (␥HV68) occurs as an acute phase of replication in several organs, which is cleared after 16 days, followed by a latent phase that is limited largely to B cells, macrophages, and dendritic cells and lasts for the life of the animal (13,15,35,39,40,42,43). Previous studies have indicated that all T-and B-cell subsets are important for control of both acute and latent ␥HV68 infection. This has been demonstrated for T cells by evaluating mice that lack both CD8 ϩ and CD4 ϩ T cells; such mice do not control acute replication and die by around 25 days after infection. On the other hand, single T-cell deficiency is less detrimental. For example, major histocompatibility complex (MHC) class II Ϫ/Ϫ or CD8 Ϫ/Ϫ mice, or mice immunodepleted of either CD4 ϩ or CD8 ϩ T cells, have only slight delays in clearance of acute replication (14). The situation during chronic infection is similar in that both virus-specific, CD4ϩ -T-cell-dependent antibody (Ab) (17, 21) and CD8 ϩ T cells (20,35) have been shown to regulate latency, and MHC class II Ϫ/Ϫ animals succumb to a wasting disease (6) and vasculitis (41), diseases that are both associated with persistent virus replication. Thus, both T-cell subsets have important roles in preventing disease associated with chronic infection.Attempts have been made to augment the immune response to latent ␥HV68 infection by priming CD8 ϩ T-cell responses against defined lytic (4, 32) or latent (36, 37) antigens. The principal aim of these studies was to assess the potential of CD8 ϩ T cells primed against single antigens to reduce latent infection. Two outcomes were reported. After induction of immunity by heterologous priming with a vaccinia virus expressing the epitope of the latency-associated M2 protein, no reduction in acute replication was observed while early latency (16 days after infection) was significantly reduced; this effect was only transient, as long-term latency (Ͼ21 days) was the...
Confusion still exists in the diagnosis of drug-induced immune haemolysis (DIH). The aim of this study was to demonstrate antibodies specific to 5-fluorouracil (5-FU) in a patient with fatal immune haemolysis (IH). The case of a patient who died due to protracted IH is described. A 57-year-old female underwent treatment with oxaliplatin, 5-FU and folinic acid due to cholangiocarcinoma. Following drug administration, she was transfused because of a mild non-haemolytic anaemia and died following haemolysis. Serological testing including antibody screening, direct antiglobulin test and detection of drug-dependent antibodies was performed using standard techniques. The patient's serum was observed to be red in colour due to the presence of free haemoglobin prior to and following blood transfusion, and contained antibodies reactive with RBCs only in the presence of urine from several patients treated with 5-FU (ex vivo antigens). Drug-induced immune haemolysis (DIH) and metabolite-dependent antibodies should always be taken into consideration when a patient being administered any type of drug develops haemolysis.
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