肾移植受者外周血中人疱疹病毒6型

为了检测人疱疹病毒６型（ＨＨＶ－６）在器官移植中的致病性甲状作者对１２例肾脏移植受者在经基础免疫治疗３周后，取外周血淋巴细胞与脐血淋巴细胞共同培养。结果显示，２例受示标本中见有细胞病变（ＣＰＥ），其中１株病毒经多次传代冻存后仍能产生ＣＰＥ。该杂细胞超薄切片电镜下风疱疹病毒样颗粒，感染细胞涂片抗ＨＨＶ－６单克隆抗体产生明显荧光，证实为ＨＨＶ－６。作者认为，ＨＨＶ－６可能在肾脏移植后感染，尤其在排斥反     

Isolation of a new human herpesvirus producing a lytic infection of helper (CD4) T-lymphocytes in peripheral blood lymphocyte cultures--another cause of acquired immunodeficiency?

A new human helper (CD4) T-lymphotropic herpesvirus (HTLHV) was first isolated in February 1985 from the cultured peripheral blood lymphocytes (PBL) of a patient with the acquired immunodeficiency syndrome, and subsequently from the PBL of 1 patient with hairy cell leukaemia and 2 patients with lymphoproliferative disease associated with human T-lymphotropic virus type I infection. The viruses could be serially subcultured in umbilical cord PBL cultures in which they infected helper (CD4) T-lymphocytes producing multinucleate giant cells with intranuclear inclusions followed by cell lysis. Electron microscopy of infected cultures revealed that the isolates were herpesviruses. Specific DNA probing showed that the 4 isolates were related to one another but were distinct from cytomegalovirus, Epstein-Barr virus, Herpesvirus hominis types 1 and 2, and varicella-zoster virus. HTLHV lyses the same target cell as human immunodeficiency virus in PBL cultures suggesting that it may have a similar potential to cause acquired immune deficiency. The development of an unequivocally diagnostic serological test is a priority, so that the epidemiology and pathogenesis of HTLHV infection can be studied.     

淋巴细胞对子宫内膜蜕膜化及胚胎着床的影响

目的　探讨淋巴细胞对子宫内膜蜕膜化及胚胎着床的影响。　方法　分离育龄妇女增殖晚期子宫内膜间质细胞 ,加入雌二醇 (E2 )、孕酮 (P)使蜕膜化后 ,加入人非孕及早孕外周血淋巴细胞与小鼠第 4天胚胎共培养 ,观察间质细胞及胚胎的孵化、粘附、扩展生长情况 ,并测定培养液中泌乳素 (PRL)含量。　结果　早孕淋巴细胞对子宫内膜蜕膜化有明显促进作用 ,特异性促进PRL分泌 (P <0 .0 5 )。淋巴细胞能促进胚胎在子宫内膜间质细胞的孵化、粘附、扩展性生长 ,早孕组胚胎扩展生长率显著高于非孕组 (P <0 .0 5 )。　结论　早孕淋巴细胞可能通过促进E2 、P激素调节蜕膜化的子宫内膜分泌PRL而促进胚胎着床。     

Recognition of virally transformed cells by lymphocytes from patients with prostatic cancer.

Data presented describe the first assay using human peripheral blood lymphocytes (PBL) against two unique virally transformed cell lines in vitro. Human cells transformed by a cytomegalovirus (CMV-Mj) isolated from normal human prostate tissue were used as target cells in microcytoxicity assays with lymphocytes from 100 patients. Three target cell types were used: control human embryonic lung cells (HEL), transformed HEL cells (CMV-Mj-HEL-2), and transformed HEL cells retrieved from tumors induced in athymic nude mice (CMV-Mj-HEL-2, T-1) by injection of CMV-Mj-HEL-2 cells. PBL preparations from 84% of all patients tested significantly killed CMV-Mj-HEL-2, T-1 cells. However, only PBL from patients with prostatic carcinoma were cytotoxic for CMV-Mj-HEL-2 cells significantly more often than for control HEL. The implications of this approach are discussed.     

Monitoring of cardiac graft recipients: comparison of in vivo activated,committed T lymphocytes in peripheral blood and in the graft

The proliferative and cytotoxic capacity of peripheral blood lymphocytes (PBL) and the cytotoxic activity of lymphocytes propagated from endomyocardial biopsies (EMB) towards donor cells was used to identify in vivo activated, committed T cells. A series of 39 PBL samples and 38 EMB simultaneously taken from 20 patients after heart transplantation was cultured in interleukin 2 (IL-2) conditioned medium. The cytotoxic capacity of these cultures against donor cells was tested in a 4-h chromium-51 release assay. From a comparable patient group, 224 samples were evaluated for donor reactivity by a primed lymphocyte test (PLT). Analysis showed that PBL cultures hardly ever contained committed cytotoxic T lymphocytes (cCTL, 2/39) or committed proliferative T lymphocytes (cPTL, 1/224). In contrast, significantly more EMB cultures (17/38, P < 0.001, χ² test) demonstrated donor-directed cytotoxicity. This was especially found during rejection (11/17 vs 6/21 without rejection, P = 0.05). These results show that after heart transplantation, committed cells are mainly found in the graft.     

Antitumor Killer Lymphocytes in the Peripheral Blood of a Patient with Transitional Cell Carcinoma of the Bladder

Background: Peripheral blood lymphocytes (PBL) from patients with bladder cancer also contain cells possessing cytotoxic activity against autologous tumor cells. These cells are phenotypically heterogenous and include natural killer (NK) and cytotoxic T cells. This study investigated the role of cytotoxic lymphocytes directed against autologous bladder cancer cells.
Methods: PBL were obtained at intervals before and after surgery and analyzed for cytotoxic activity against autologous bladder cancer cells in 4-hour⁵¹ Cr release assay. PBL stimulated with autologous tumor cells were also transformed with human T-lymphotropic virus type-1, establishing a cell line (KB31) which was analyzed for phenotype and cytotoxic activity against the autologous tumor cells.
Results: PBL preoperative cytotoxic activity was low, but increased after surgery. Cytotoxic activity was found not only against autologous bladder cancer cells, but also against heterologous bladder cancer (KK-47) and myeloid leukemia (K562) cells, with the highest activity against the heterologous cell lines. The cytotoxic activity of KB31 was 40|X% against autologous tumor cells 6 weeks after initiation of the cell line, but decreased to 5|X% by 6 months. This activity was lower than that against the other cell lines, and was similar to that of PBL in short-term culture. Fluorescence-activated cell sorter (FACS) analysis demonstrated that in KB31 cells at 6 weeks, CD8+ cells were dominant, but CD56+ cells predominated at 6 months.
Conclusion: These results suggest that the presence of cytotoxic activity in the peripheral blood of the patient was due to both cytotoxic T cells and NK cells. The cytotoxic activity was lowest prior to surgery and increased postoperatively.     

The regulation of natural killer cell activity by splenic nonspecific suppressor cells and its modification in cancer patients

Spleen cells (SC), splenic venous blood lymphocytes (SVL) and peripheral blood lymphocytes (PBL) from gastric and esophageal cancer patients were simultaneously tested for natural killer (NK) and nonspecific suppressor (Ts) cell activities. Furthermore, the influence of Ts activity on the augmentation of NK activity by a biological response modifier (BRM) was also investigated. Positive Ts activities were frequently detected in the SC, SVL and PBL of advanced cancer patients. The NK activities of SC and SVL were maintained even in advanced cancer patients, though significantly depressed NK activities were observed in the PBL of advanced cases. Cancer patient SC, SVL and PBL with positive Ts activity showed low NK activities. Moreover, the NK activities of SVL and PBL were low in the patients with positive Ts activity in SC. The NK activity of normal control PBL was strongly augmented by interleukin 2, interferon and OK-432. These BRMs exhibited comparable capacities to augment the NK activities of SC, SVL and PBL with negative Ts activity in cancer patients, however, the effects of these agents seemed to be low in cells with a positive Ts activity. These results suggested that NK activity might be regulated by nonspecific suppressor cells and the presence of suppressor cells might affect the augmentation of NK activity through BRM in circulating blood lymphocytes and also in spleen cells.     

The regulation of natural killer cell activity by splenic nonspecific suppressor cells and its modification in cancer patients

Spleen cells (SC), splenic venous blood lymphocytes (SVL) and peripheral blood lymphocytes (PBL) from gastric and esophageal cancer patients were simultaneously tested for natural killer (NK) and nonspecific suppressor (Ts) cell activities. Furthermore, the influence of Ts activity on the augmentation of NK activity by a biological response modifier (BRM) was also investigated. Positive Ts activities were frequently detected in the SC, SVL and PBL of advanced cancer patients. The NK activities of SC and SVL were maintained even in advanced cancer patients, though significantly depressed NK activities were observed in the PBL of advanced cases. Cancer patient SC, SVL and PBL with positive Ts activity showed low NK activities. Moreover, the NK activities of SVL and PBL were low in the patients with positive Ts activity in SC. The NK activity of normal control PBL was strongly augmented by interleukin 2, interferon and OK-432. These BRMs exhibited comparable capacities to augment the NK activities of SC, SVL and PBL with negative Ts activity in cancer patients, however, the effects of these agents seemed to be low in cells with a positive Ts activity. These results suggested that NK activity might be regulated by nonspecific suppressor cells and the presence of suppressor cells might affect the augmentation of NK activity through BRM in circulating blood lymphocytes and also in spleen cells.     

Role of natural killer T (NKT) cells lacking interleukin (IL)-4 producing abilities on the CC-chemokine ligand 2-associated herpes simplex virus type 1 infection in human severe combined immunodeficiency (SCID) mouse chimeras

CC-chemokine ligand 2 (CCL2/monocyte chemoattractant protein 1) is known to have an important role on T helper type 2 (Th2) cell generation and described to induce interleukin (IL)-4 production by activated T cells. In the present study, an increase of CCL2 production in cultures of peripheral blood lymphocytes (PBL) from patients with severe thermal injuries was demonstrated. Severe combined immunodeficiency (SCID) mice reconstituted with PBL from healthy donors (PBL-SCID chimeras) were resistant to infection with herpes simplex virus type 1 (HSV-1). Treatment of these chimeras with recombinant human CCL2 resulted in an increased susceptibility to the same HSV-1 infection. However, human SCID mouse chimeras created by PBL depleted of natural killer T (NKT) cells (NKT(-) PBL-SCID chimeras) were resistant to HSV-1 infection, even though they were treated with CCL2. IL-4 was not detected in the sera of NKT(-) PBL-SCID chimeras treated with CCL2, while IL-4 was detected in the sera of PBL-SCID chimeras under the same CCL2 administration. NKT cells isolated from PBL were shown to be cells not responsible for CCL2-stimulated IL-4 production. However, in the presence of CCL2, IL-4 was detected in culture fluids of NKT cells co-cultured with naive T cells. This cytokine was produced in co-cultures of NKT cells pretreated with CCL2 (CCL2-NKT cells) and naive T cells. In addition, IL-4 production was demonstrated in transwell cultures of CCL2-NKT cells and naive T cells. These results suggest that NKT cells lacking IL-4 producing abilities contribute to the CCL2-associated increase in the susceptibility of thermally injured patients to HSV-1 infection through the induction of Th2 cell generation.     

Activation by the protein-bound polysaccharide PSK (krestin) of cytotoxic lymphocytes that act on fresh autologous tumor cells and T24 human urinary bladder transitional carcinoma cell line in patients with urinary bladder cancer

PSK, a protein-bound polysaccharide Kureha, was tested for its ability to modulate the cytotoxicity of lymphocytes that act on autologous tumor cells and T24 human urinary bladder tumor cells in urinary bladder cancer patients in a 6-h 51Cr release assay. In vitro treatment of peripheral blood lymphocytes (PBL) with PSK for 18 hours resulted in an augmentation or induction of cytotoxicity against relatively resistant T24 cells in previously reactive and nonreactive cases, respectively. The PSK-treated PBL were able to kill more effectively tumor cells that were freshly isolated from the same cancer patients than non-treated PBL. The effects of PSK were noted with PBL as well as tumor infiltrating lymphocytes (TIL) and with PSK at concentrations of 10 to 100 micrograms./ml., while PSK at higher doses reduced their lytic activities. The addition of PSK to the assay at the same concentrations also enhanced the cytotoxicities. Autologous tumor killing (ATK) activities of both large granular lymphocytes (LGL) and T lymphocytes were enhanced by PSK. Treatment of PBL with PSK did not effect on the proportion of PBL binding to the tumor cells, while it augmented the cytotoxic activity. Cell-free supernatant of PSK-stimulated lymphocyte culture did not contain any detectable amounts of interferon-alpha (IFN-alpha), interferon-gamma (IFN-gamma) and interleukin-2 (IL-2). In addition, anti-IFN-alpha monoclonal antibody (MAb), anti-IFN-gamma MAb and anti-IL-2 MAb did not inhibit PSK-induced augmentation of cytotoxicity against T24. Oral administration of PSK (three gm./day) to patients with urinary bladder cancer daily for seven days before operation resulted in an augmentation of the cytotoxicity against T24 cells in five out of 10 patients and no change of the cytotoxicity in the other five patients. ATK activity was also enhanced by oral administration of PSK in three out of five patients. These results indicate that the antitumor activity of PSK may be in part mediated through activation of tumor killing system independent of IFN-alpha, IFN-gamma and IL-2.     

Adriamycin-mediated potentiation of cytotoxicity against freshly isolated bladder cancer cells by autologous non-activated peripheral blood lymphocytes and tumor infiltrating lymphocytes

PURPOSE: Previous studies indicated that cancer patients lack functional anti-tumor cytotoxic lymphocytes. However, anti-tumor cytotoxic lymphocytes may coexist with immunoresistant tumor cells. We reasoned that anti-tumor cytotoxic activity of lymphocytes may be revealed if the tumor cells are sensitized to killing. It has been reported that adriamycin (ADR) exhibits various immunomodulating activities. In the present study, we investigate the effect of ADR on the susceptibility of freshly isolated bladder cancer cells to lysis by autologous non-activated peripheral blood lymphocytes (PBL) and tumor infiltrating lymphocytes (TIL). MATERIALS AND METHODS: Cytotoxicity was determined by a 1-day microculture tetrazolium dye assay. RESULTS: Treatment of ADR-resistant fresh bladder cancer cells with ADR at 0.1 microg./ml. or more for 3 hours or more enhanced their susceptibility to lysis by autologous PBL. This ADR-induced enhancement of susceptibility of fresh bladder cancer cells to lysis by PBL was also observed when lymphokine activated killer cells, purified natural killer cells and T lymphocytes were used as effector cells. Furthermore, while cytotoxicity of freshly derived TIL against autologous bladder cancer cells was minimal, significant cytotoxicity was observed with ADR-treated bladder cancer cells. The ADR analogs, epirubicin and pirarubicin, also enhanced the susceptibility of bladder cancer cells to lysis by autologous PBL. Treatment of bladder cancer cells with ADR had no effect on the expression of MHC class I on the cancer cells or the frequency of bladder cancer target cell conjugates to autologous PBL. Treatment of bladder cancer cells with ADR augmented their sensitivity to anti-Fas monoclonal antibody and tumor necrosis factor-a. Pretreatment of effector cells with ADR had no effect on their cytotoxic function. CONCLUSIONS: These findings demonstrate that PBL and TIL in patients with bladder cancer exhibit anti-tumor cytotoxic function, but their function is not manifested due to development or acquisition of tumor cell resistance to killing. However, the resistance of bladder cancer cells to killing by cytotoxic lymphocytes is overcome if cancer cells are sensitized by subtoxic concentrations of ADR. These findings suggest that treatment of bladder cancer patients with low doses of ADR may sensitize the cancer cells to killing by autologous circulating and tumor infiltrating lymphocytes and may be a novel immunotherapeutic modality for the treatment of drug-resistant and/or immune-resistant bladder cancer.     

In vitro killing of human glioblastoma by interleukin-2-activated autologous lymphocytes

Culture of peripheral blood lymphocytes (PBL) from brain-tumor patients with recombinant interleukin-2 (IL-2) results in the activation of lymphokine-activated killer cells (LAK) with the capacity to lyse autologous and allogeneic glioblastoma. In this study, PBL obtained from brain-tumor patients were cultured with or without IL-2 for 3 to 7 days and then tested for their ability to lyse target cells in a 4-hour chromium release cytotoxicity assay. The PBL were drawn 1 to 2 weeks following operative tumor debulking. Cells used as targets included fresh brain-tumor cells obtained at the time of craniotomy, fresh brain-tumor cells grown from 1 to 3 weeks in tissue culture, fresh autologous PBL, and allogeneic glioblastoma cells grown in tissue culture. Peripheral blood lymphocytes from brain-tumor patients that were cultured without IL-2 did not significantly lyse autologous or allogeneic glioblastoma. However, when these PBL were cultured with IL-2, LAK were generated which produced marked lysis of autologous as well as allogeneic tissue-culture glioblastoma in all of eight cases. Significant lysis of autologous fresh tumor by patient LAK was observed in four of five experiments. By contrast, patient LAK did not kill autologous normal PBL. The ability to generate LAK was not influenced by the patient's age, previous therapy, or the administration of steroids.     

Enhanced cytolytic activity of intestinal intraepithelial lymphocytes in patients with Crohn’s disease

Background and aims: Dysfunction of the immune system with inappropriate responses of lymphocytes to various antigens has been implicated in the development of Crohn’s disease. Therefore, the functional and phenotypic characteristics of intestinal intraepithelial lymphocytes (IEL) in comparison to peripheral blood lymphocytes (PBL) were analyzed in patients with and without Crohn’s disease. Patients and methods: Six patients with Crohn’s disease and six control patients were studied. Isolated IEL and PBL were tested for cytolytic activity against the human adenocarcinoma cells DLD-1 and the human leukemia cells K562 in a ⁵¹Cr-release assay. Two-color flow cytometry was performed for phenotype analysis of isolated lymphocytes. Results: IEL from patients with Crohn’s disease showed significantly increased cytolytic activity against epithelial-derived target cells when compared with IEL from control patients. In contrast, no functional changes were detectable among PBL from patients with Crohn’s disease. IEL from patients with Crohn’s disease contained a significantly higher percentage of CD8⁺ lymphocytes when compared with IEL from control patients, whereas no phenotypic changes were observed among PBL. Conclusions: In Crohn’s disease, the functional and phenotypic changes of T cells are limited to lymphocytes of the intestinal mucosa. Furthermore, it is conceivable that the increased cytolytic activity of IEL contributes to the tissue damage in this disease. Received: 22 September 1999 In revised form: 25 February 2000 Accepted: 28 February 2000     

Recognition of islet-directed peripheral blood lymphocytes in vitro before rejection of allogeneic grafted islets

A co-culture of splenic lymphocytes with allogeneic pancreatic islets [i.e., mixed lymphocyte islet co-culture (MLIC)] for 96 hr leads to reduction of beta-cells and to an allospecific induction of major histocompatibility complex (MHC) class II antigens on beta-cells. The intent of our investigation was to determine whether peripheral blood lymphocytes (PBL) obtained from allogeneic islet-grafted BB/OK rats (=sensitization in vivo) cause similar alterations to donor-specific islet cells. PBL prepared before transplantation, before (at day 7) and after islet rejection were co-cultured for 24 hr with donor-specific islets. PBL obtained at any time before and after transplantation caused reduction of beta-cells and enhancement of intercellular adhesion molecule-1(+)/beta-cells. Induction of MHC class II+ beta-cells was most pronounced with PBL obtained before rejection. Down-regulation of major histocompatibility complex class I+ beta-cells was caused by PBL that had been obtained from grafted animals only; it was most pronounced before islet rejection and has never been observed with lymphocytes from nongrafted normoglycemic rats. The 24-hr MLIC is capable of recognizing functionally active, donor-specific lymphocytes and is able to distinguish between the effects of sensitized and nonsensitized lymphocytes.     

Porcine endogenous retrovirus encodes xenoantigens involved in porcine cellular xenograft rejection by mice

BACKGROUND: Identification of the antigens that stimulate transplant rejection can help develop graft-specific antirejection strategies. The xenoantigens recognized during rejection of porcine cellular xenografts have not been clearly defined, but it has been assumed that major histocompatibility complex (MHC) xenoantigens are involved. METHODS: The role of porcine endogenous retrovirus (PERV) as a source of xenoantigens was examined. The authors used morphometry to compare the kinetics of swine leukocyte antigen (SLA) pig thyroid xenograft rejection in control mice and mice immunized with PERV PK15 cells (porcine kidney epithelial cells), PERV SLA pig peripheral blood lymphocytes (PBL), PERV virions purified from PK15 cells, and PERV or PERV A pseudotypes produced from infected human 293 cells. The tempo of rejection for cellular xenografts of PERV A pseudotype-producing human 293 cells, uninfected human 293 cells, and PK15 cells in PERV-preimmunized and control mice was also compared. RESULTS: Mice immunized with PK15 cells rejected pig thyroid xenografts significantly faster at day 5 than control mice and mice immunized with pig PBL. This correlated with the amount of PERV RNA and virions produced, but not with the amount of SLA class I MHC expressed by PK15 cells. Immunization of mice with PERV virions purified from porcine PK15 cells and with PERV virions or PERV A pseudotypes produced by human 293 cells also induced accelerated xenograft rejection by 5 days. Accelerated rejection induced by virus pretreatment was CD4 T-cell dependent and restricted to PERV-expressing cellular xenografts of porcine or nonporcine origin. CONCLUSIONS: PERV acts as a significant source of xenoantigens that target porcine cellular xenografts for rejection.     

Identification and expansion of human lymphokine-activated killer cells: implications for the immunotherapy of cancer

Immunotherapy with lymphokine-activated killer (LAK) cells and interleukin 2 (IL-2) has been demonstrated to cause the regression of some human tumors. Expansion of peripheral blood lymphocytes (PBL) in recombinant or naturally produced IL-2, mitogens, and feeder cells results in a progressive expansion of cell number but a decline in lytic activity with time. Lytic activity for fresh tumor is best generated in IL-2 alone from specific purified subpopulations of lymphocytes. The precursor of the LAK cell has been isolated from a nonadherent, sheep erythrocyte receptor negative (E-) lymphocyte subpopulation by the selection of Leu 11+ and Leu 15+ cells by cell sorting. Separation resulted in a significant increase (P2 less than 0.05) in lytic activity against fresh tumor by the separated 11+15+ lymphocytes compared to the 11-/15- lymphocytes or PBL. Leu 11+/15+ lymphocytes could be expanded up to eightfold in IL-2 alone with maintenance of lytic activity. We identified two surface antigens on the LAK precursor cell, Leu 15 and Leu 11, and demonstrated a technique for obtaining purified populations of these cells. Purified and expanded LAK cells when administered to patients may have a role in increasing the potency and decreasing the toxicity associated with this therapy.     

Phenotypic expression of bronchoalveolar lavage cells in lung rejection and infection

The differentiation of episodes of lung allograft rejection from infection continues to be a problem. Bronchoalveolar lavage (BAL) has recently gained some success in the diagnosis and management of interstitial lung disease. To assess the usefulness of BAL in differentiating between lung allograft rejection and infection, we examined the differences in cellular subsets of BAL and peripheral blood (PBL) samples in a controlled canine model of rejection or pneumonia. Single-lung allotransplants were allowed to undergo rejection by withdrawing immunosuppressive agents (n = 6). In another group of dogs (n = 5), pneumonia was induced by transbronchial injection of Pseudomonas aeruginosa and melted agar followed by bronchial fulguration. Cells obtained from bronchoscopic BAL and PBL samples were labeled with functionally characterized cross-reactive murine monoclonal antibodies. Transthoracic needle biopsies and transbronchial biopsies were done to assess their adequacy in examining the rejecting or infected lungs and were compared with open lung biopsies. We found the following: (1) the percentage of DT2-labeled cells was significantly higher (p less than 0.05) in BAL samples from rejecting lungs compared with infected lungs; (2) the PBL/BAL ratio of DT2-labeled cell percentages was significantly higher in pneumonia (1.7 +/- 0.3) than rejection (0.5 +/- 0.2) (p less than 0.004); (3) the percentage of E11-labeled cells in PBL samples was significantly higher (p less than 0.02) in rejection than in infection; and (4) the ratio of WIG4 to DT2 cellular subset percentages in BAL samples from rejection (26.8 +/- 9.9) was significantly lower than from infection (61.0 +/- 22.9) (p less than 0.03). Transthoracic and transbronchial biopsies did not always yield representative specimens.(ABSTRACT TRUNCATED AT 250 WORDS)     

Circulating Epstein‐Barr virus DNA to monitor lymphoproliferative disease following pediatric liver transplantation

Abstract Epstein‐Barr virus (EBV) infection can induce uncontrolled lymphocyte B proliferation in immunosuppressed transplant patients. Monitoring circulating EBV‐infected lymphocytes can help in identifying patients at risk of post‐transplant lymphoproliferative disease (PTLD). Circulating EBV genome levels were determined in 54 liver transplant pediatric recipients. Ten patients had more than 500 EBV genome/10⁵ peripheral blood lymphocytes (PBL) and exhibited clinical manifestations of EBV infection; three developed PTLD. To treat EBV infection, the level of immunosuppression was reduced and acute rejection developed in 4 patients. Three were treated with steroid and one had to be switched from cyclosporine to tacrolimus. Treatment of acute rejection was associated with increases in circulating EBV genome. None of the patients with less than 500 EBV genome/10⁵ PBL developed PTLD or EBV infection. Monitoring of EBV DNA is useful in the management of EBV infection and PTLD following pediatric liver transplantation. EBV infection should be treated in ways which do not expose patients to the risk of rejection.     

The activity of immunologic cells from peripheral blood, splenic venous blood and spleen in patients with advanced gastric cancer. A comparative study]

To elucidate the immunologic function of the spleen in AGC patients, peripheral blood lymphocytes (PBL), splenic venous blood lymphocytes (SVL) and spleen cells (SC) from 40 patients were tested for NK cell activity and T-cell subsets. Significant impairment of NK cell activity, decreased rate of CD+3 and CD+4 cells, declined CD+4/CD+8 ratio, and increased CD+8 cells were noted in SC of AGC patients as compared with PBL of normal subjects. NK cell activity and CD+4 cells of SVL and SC were significantly lower than those of PBL in AGC patients. More significant decline of CD+4/CD+8 cell ratio was found in SVL and SC when compared with PBL in AGC, mainly as a result of the marked decrease of CD+4 cells in SC. In conclusion, AGC tends to weaken the immune status of patients and the immunosuppressive role of the spleen would become more evident with the development of the tumor.     

Long-term survival of heart grafts in the presence of donor-pecific cytotoxic T-cell precursors (CTLp) in the peripheral blood

Abstract To monitor their immunological status we determined donor and third-party-pecific cytotoxic T-cell precursor frequencies (CTLpf) in the peripheral blood of 15 heart transplant recipients. PBL samples were obtained at different time points before and after transplantation. Donor-pecific CTLpf and third-party-pecific CTLpf were within the same range for all samples (1–1489/106 cells). The donor-pecific CTLpf were not different between patients who had never had an acute rejection (AR) and patients who had an acute rejection as diagnosed by endomyocardial biopsy (EMB). No difference was' observed between donor-pecific CTLpf of samples taken on the day of transplantation and those obtained between 3 months and 3 years after transplantation. There was also no relationship between the donor-pecific CTLpf in the PBL and the culturing success of lymphocytes from EMB taken at the same time. CTLpf were in the same range both when cultures could be propagated from the graft and when no cells grew out. We conclude that long-term graft survival is possible in the presence of CTLpf in peripheral blood.