OKT8 Cells Research Articles

Reciprocal conditioning: T cells as regulators of dendritic cell function

Reciprocal conditioning: T cells as regulators of dendritic cell function

Treatment of postoperative gastric cancer with the Fuzheng Huoxue anticancer prescription.

To study effects of the Fuzheng Huoxue anticancer prescription (Traditional Chinese Medicine) in treatment of gastric cancer. Sixty-nine patients with histologically confirmed mid- or late-stage gastric cancer were assigned to two groups. The treatment group included 35 cases (26 males and 9 females; 2 patients aged 33-40 years, 18 patients aged 41-60 years, and 15 patients aged 61-75 years; mean group age = 58.4 years). The control group included 34 cases (23 males and 11 females; 4 patients aged 33-40 years, 16 patients aged 41-60 years, and 14 patients aged 61-75 years; mean group age = 56.8 years. The two groups were not significantly different in sex, age, their clinical and pathological stages of disease or operation mode. The two groups of patients were given similar treatments; however, patients in the treatment group were given the Fuzheng Huoxue anticancer prescription. In animal studies, SGC-7901 gastric cancers cells were inoculated into the backs of 30 nude mice under sterile conditions. After inoculation, the nude mice were randomly allocated to a control group, a traditional Chinese medicine group, and a chemotherapy group (n = 10 mice per group). The total weight of the 10 mice in each group was similar. Each nude mouse in the control group received 0.5 mL of saline solution each day. Mice in the traditional Chinese medicine group received 0.5 mL of the Fuzheng Huoxue anticancer prescription (containing 1.5 g crude drug) each day, while mice in the chemotherapy group were intraperitoneally injected with 1 mg of 5-Fu once a week for 8 wk. Prior to treatment, the mean OKT8 percentage among gastric patients in the treatment group was 45.94% ± 8.45%, the mean OKT4/OKT8 ratio was 0.89 ± 0.19, the mean AT-III concentration was 29.9 ± 7.9 mg/dL, the mean Fa value was 50.4% ± 24.4%, and the mean β-TG concentration was 91.0 ± 25.9 ng/dL. Prior to treatment, the mean percentage of OKT8 cells among patients in the control group was 49.21% ± 6.60%, the OKT4/OKT8 ratio was 0.94 ± 0.20, the AT-III concentration was 32.3 ± 7.2 mg/dL, the mean Fa value was 57.3% ± 24.6%, and the mean β-TG concentration was 87.5 ± 34.2 ng/dL. After treatment, the mean OKT8 percentage among patients in the treatment group was 33.52% ± 7.80%, the mean OKT4/OKT8 ratio was 1.47 ± 0.51, the mean AT-III concentration was 38.8 ± 5.5 mg/dL, the mean Fa value was 102.6% ± 31.6%, and the mean β-TG concentration was 62.3 ± 15.1 ng/dL. After treatment, the mean OKT8 percentage among patients in the control group was 42.22% ± 7.07%, the mean OKT4/OKT8 ratio was 1.12 ± 0.24, the mean AT-III concentration was 30.9 ± 8.0 mg/dL, the mean Fa value was 64.6% ± 26.9%, and the mean β-TG concentration was 67.0 ± 42.1 ng/dL. These data indicate that after treatment, the immunologic function of the T lymphocytes of gastric cancer patients in the treatment group was significantly improved (P < 0.01). Additionally, the hypercoagulability in the treatment group was also improved (P < 0.001), and the mean OKT4/OKT8 ratio, antithrombin III (AT-III) concentration, and fibrinolytic activity, etc. had all beome normalized. The one-year (86%), 3-year (69%), and 5-year (40%) survival rates in the treatment group were all higher than those in the control group (P < 0.05). The mean tumor weights in the control, traditional medicine, and chemotherapy groups were 0.895 ± 0.289 g, 0.433 ± 0.177 g, and 0.357 ± 0.142 g, respectively. The tumor-inhibition rates in the traditional Chinese medicine group and chemotherapeutic group (51.6% and 60.1%, respectively) were significantly better than that in the control group (P < 0.001). The mean tumor weight in the traditional Chinese medicine group (24.68 ± 1.93 g) was significantly higher than that in both the treatment group (22.96 ± 1.87 g) and control group (22.47 ± 2.18 g). The Fuzheng Huoxue anticancer prescription can not only replenish vital functions (Zhengqi), correct a hypercoagulatory state, improve immunologic function, and extend patient survival times, but may also directly inhibit gastric tumor growth without producing toxic side effects.

Encapsulation of OKT3 cells in hollow fibers.

Encapsulation of an OKT3 cell line in hollow fibers was evaluated in vitro and in vivo. The cell line is a mouse hybridoma producing immunoglobulin G2a (IgG2a) against CD3 human T lymphocytes and thus may function as a nonspecific activation system of a subpopulation of human T lymphocytes. For encapsulation purpose, hollow fibers of polypropylene K600 PP Accurel (Akzo, Germany) were selected. Hollow fibers were siliconized to improve membrane biocompatibility for in vivo experiments. The siliconized hollow fibers exhibited acceptable diffusive permeability (P) [ml/min/m2] for small solutes (for creatinine, p = 63.9 +/- 2.0, n = 3) and larger solutes (for albumin, p = 16.9 +/- 1.9, n = 3; for IgG, p = 1.0 +/- 0.2, n = 3). The 12 cm long hollow fibers were filled with a suspension of OKT3 cells of an average density of 10(6) cells/ ml, and both ends were sealed. The encapsulated cells were cultivated in RPMI 1640/10% CS medium at 37 degrees C, 5% CO2 for a period of 3 to 4 days. After the culture period, the medium was tested on human peripheral blood lymphocytes for the presence of anti-CD3 antibody and read in a flow FACS-trac cytometer (Becton Dickinson Immunocytochemistry Systems, San Diego, CA). The tightness of hollow fiber sealing was tested with a bubble point method. The number of cells increased after cultivation by four- to nine-fold on average (n = 11). Ten experiments were performed in vivo with OKT3 cells encapsulated in hollow fibers and implanted subcutaneously into mice for 3 days. In 50% of the experiments, some anti-CD3 antigens on human lymphocytes were found; however, the difference, in comparison with control, in percent of CD3+ was insignificant. In conclusion, the hollow fiber method for cultivation of hybridoma cells in vitro allows for separation of cells from the medium containing secreted anti-CD3 antibodies and is effective in maintaining cell viability. In vivo application needs additional study.

The potential role of xenogeneic antigen‐presenting cells in T‐cell co‐stimulation

Abstract: CTLA4‐Fc is a chimeric murine construct consisting of the CD28 homologue CTLA4 and the constant portion of the heavy chain of mouse IgG2a, with a potential to suppress cellular xeno‐immune responses. The aim of this study was to determine the degree of binding of CTLA4 to B7 ligands on cells of different species and to use CTLA4‐Fc as a tool for the study of cross‐species CD28‐B7 interactions. As assessed by flow cytometry, CTLA4‐Fc bound to mouse L‐cells and human Epstein Barr virus (EBV) transformed lymphoblastoid cells and concanavalin A (Con A) or LPS‐stimulated peripheral blood mononuclear cells (PBMC) or splenocytes from rat, dog, and pig. CTLA4‐Fc inhibited the proliferation of Con A‐stimulated PBMC or splenocytes from mouse, rat, dog, and pig, in a dose‐dependent fashion with approximately 80% inhibition at a concentration of 10 μg/ml. It did not inhibit the proliferation of Con A‐stimulated human PBMC, although it did inhibit the human versus human, and human versus pig primed mixed lymphocyte culture (MLC) in a dose‐dependent fashion. At submitogenic concentrations, purified human T‐cells did not proliferate after incubation with Con A alone. However, proliferation occurred with the addition of B7 positive L‐cells or pig PBMC, but not B7‐negative OKT4 cells. Furthermore, CTLA4‐Fc inhibited proliferation in a dose‐dependent fashion. CTLA4‐Fc bound to all species tested and resulted in inhibition of Con A‐stimulated proliferation in these species, except for humans. Human T‐cells proliferated in response to co‐stimulation with xenogeneic B7, and this could be inhibited by CTLA4‐Fc, suggesting that xenogeneic B7 was capable of providing a functionally significant co‐stimulatory signal necessary for human T cell activation in vitro.

Connection of atopic disease in Japanese patients with juvenile dermatomyositis based on serum IgE levels

Serum IgE levels of 22 patients with juvenile dermatomyositis (JDMS), 44 normal children, and 43 patients with adult dermatomyositis were compared. The geometric mean of serum IgE levels was significantly higher in the juvenile patients when compared with normal children (p < 0.01) and adult patients (p < 0.01). Of the 22 patients with JDMS, 11 (50%) had elevated serum IgE levels accompanied by atopic disease. Dermatomyositis was accompanied by atopic dermatitis (AD) in 9 (41%) of these 22 patients, a high prevalence when compared with reports among the general population. Following the appearance of muscular symptoms in JDMS patients with AD, the ratio of OKT4 to OKT8 cells rose due to a reduction in the percentage of OKT8-positive cells, along with further elevations in serum IgE levels and intractable cutaneous manifestations of dermatomyositis. All this may be a result of an interaction between the immuno-mechanism of this disease and that of AD. We suspect that, in general, children with impaired cell-mediated immunity, presenting with such symptoms as AD, may have a higher tendency for developing JDMS.

Pharmacokinetics of R 82913 in patients with AIDS or AIDS-related complex

R 82913, a tetrahydroimidazobenzodiazepinthione (TIBO) derivative with potent activity against human immunodeficiency virus 1 (HIV-1) in vitro, was given to 22 patients with AIDS or AIDS-related complex in a dose-escalating pilot study. Doses of 10 to 300 mg administered daily by intravenous infusion were well tolerated for up to 50 weeks, with no haematological or biochemical evidence of toxicity. Mean OKT4 cell count rose slightly during the second month of treatment when higher steady-state plasma concentrations of the drug were achieved. Median p24 antigen concentration fell by 41% during the first month of therapy. When the rise in p24 antigen before therapy was compared to the fall during treatment, end-point analysis showed a significant difference (p<0·03). The combination of potent antiretroviral activity in vitro and the observed effect on HIV p24 antigen and absence of toxicity in vivo indicate that R 82913 and related TIBO derivatives merit further study in the treatment of retroviral infections.

鼻アレルギー患者の下甲介粘膜における免疫組織学的検討 主にＴリンパ球に関して

Distribution of B lymphocytes, T lymphocytes subpopulations, activated T lymphocytes and Langerhans cells of the nasal mucosa in 28 patients with nasal allergy ranging in age from 19 years to 54 years was studied. The specimens from inferior turbinates were frozen at -70 degrees C and sliced at a thickness of 4 microns by cryostat. Monoclonal antibodies and peroxidase-antiperoxidase staining (Ortho) were used to detect these cells. OKT4, OKT8, OKT6 and OKB19 were used as markers of helper/inducer T cells, suppresser/cytotoxic T cells, Langerhans cells and B cells, respectively. OKDR was used as a marker of activated T cells, B cells, Langerhans cells and macrophages. Many OKT4 and OKT8 positive cells were observed in lamina propria. In every case, more OKT4 positive cells were detected in number than OKT8 positive cells. Some OKB19 positive cells and macrophages were observed in lamina propria, but OKT6 positive cells were not observed. OKDR positive cells were observed in high density, and more OKDR positive cells were detected than OKT4, OKT8 and OKB19 positive cells. Most of the OKDR positive cells were small in size and round in shape. From these results, many T lymphocytes were thought to be activated, and T lymphocytes were thought to play an important role in nasal allergy.

Do Calcium Channel Blockers Have Any Influence on the Immunological Status of Renal Graft Recipients on Ciclosporin Therapy?

We have assessed the peripheral distribution of T cells, using the monoclonal antibodies OKT3, OKT4, OKT8 and LEU7 and the proliferative response to phytohaemagglutinin (PHA), in 10 renal transplant recipients. In each patient, the immunological pattern was evaluated twice, both before and after 1 month of calcium antagonist (calcium channel blockers, CaA) treatment. During treatment with CaA, we have observed both a significant decrease in the mitogenic response to PHA and a significant increase in OKT8 cells. Our data support the hypothesis that CaAs per se may have an immunomodulatory effect on T cell distribution independently of changes in ciclosporin (CS) blood levels. These results could also provide a cellular basis for synergism between CS and CaA.

Enhancement of Suppressor T Cell Activity by Lymphocyte Promotiong Factor of Bordetella Pertussis

Lymphocyte promoting factor (LPF), a bioproduct of Bordetella pertussis shown previously to exert immunosuppressive effects, was examined for its effect on Concanavalin A (Con A) induced T lymphocyte suppressor activity by human lymphocytes. Suppressor cells (5 x 10(4) cells/well) first generated with Con A (10 micrograms/ml) for 24h were co-cultured with responder cells (5 x 10(4) cells/well) for another 72h in the presence of Con A (2.5, 5, 20 micrograms/ml). In this culture condition, LPF (20 micrograms) and/or histamine 10(-5) M or 10(-6) M/well were added for comparison. The suppressor activity was assessed by the reduction of the uptake of radioactivity of [3H] thymidine compared to that of Con A alone. Lymphocytes treated with LPF exhibited increase of suppression by 22 to 41%, while LPF and histamine (10(-5) M) together further increased the suppression by 35 to 63% compared to controls. Serial studies on cell population in the culture indicated OKT8(+) cells proliferated after day 6 in culture. These results indicated LPF exerts selective enhancement of T cell suppressor activity by 72h in culture, prior to cell expansion, and that activity can be further strengthened by sensitizing cells to histamine.

Allergen-specific induction of interleukin-2 (IL-2) responsiveness in lymphocytes from children with asthma: I. Antigen specificity and initial events of the induction

Interleukin-2 (IL-2) responsiveness of Dermatophagoides farinae (Df)-stimulated lymphocytes from children with bronchial asthma was studied. Six-day culture of lymphocytes from allergic patients increased after an additional 3 days of incubation with recombinant IL-2. This phenomenon was not observed when the lymphocytes of patients allergic to Df were stimulated with ovalbumin (OVA). Normal lymphocytes stimulated with Df expressed Tac antigen (low-affinity IL-2 receptor) but, in contrast to the patients' lymphocytes, did not absorb nor respond to IL-2. Nonadherent responder cells cultured with Df-pulsed autologous adherent cells acquired IL-2 responsiveness, but those cultured with OVA-pulsed adherent cells did not. The monoclonal antibody to HLA-DQ framework (Leu 10 and clonab DQ), but not to HLA-DR framework (OKIa1) and HLA-DP (HLA-DP and clonab DP-DR), blocked the antigen-presenting cells from inducing IL-2 responsiveness. Nonadherent responder cells depleted of OKT4 (CD4)-positive cells failed to acquire IL-2 responsiveness, whereas depletion of OKT8 (CD8) cells had no impact. Taken as a whole, the results indicate that DQ-bearing adherent cells from allergic donors play a key role in presenting Df antigen to allergen-specific responder T cells, which are very likely to be members of the OKT4 positive subset.

Immunoresponse of Tissue Infiltrating Lymphocytes in Bladder Tumors

Local immunocompetence was evaluated immunohistochemically in patients with bladder tumors before and after local injections of an immunomodulator. The subpopulations of tissue infiltrating lymphocytes (TIL) were examined by staining six serial sections with Leu4, Leu7, LeulO, LeuM3, OKT4, and OKT8 antibodies. T cells predominated over B cells in 19 of 25 bladder tumors. T cell infiltration was prominent around tumor cells, and it was marked in non-invasive tumors. B cells were rare in the stroma. In patients with low-stage tumors, OKT8 cells were more prominent than OKT4 cells. NK cells accumulated within cancer nests but their infiltration was scanty in invasive bladder tumors. Before surgery, immunomodulators (OK-432, IL-2) were injected intratumorally. Their administration resulted in marked increase of T and NK cells, irrespective of the stage of disease; there was a slight increase in B cells. These findings suggest that local immunosurveillance plays a role against bladder tumors. Further studies are required to elucidate host immune responses in the microenvironment of the cancer site, as well as the systemic immune reaction.

血友病患者におけるＨＩＶ関連マーカーと免疫異常

Etiological and immunological evaluations of 101 hemophiliacs treated with coagulation factor concentrates were performed. All samples were assayed for HIV antigen (Ag) with two different enzyme immunoassays (ABBOTT/VIRONOSTIKA), confirmed for antibody (Ab) to HIV with two different methods (ABBOTT ENVACOR/BIO-RAD westernblot). Results of serum HIV related markers assayed by these methods classify the patients into three groups: Of 101 patients, 37 in group A (Ab negative), 53 in group B (Ab positive but Ag negative), 11 in group C (Ab and Ag positive).OKT4 (helper/suppressor inducer) cells and OKT4/OKT8 (suppressor/cytotoxic) ratios in group C (323±164/μl and 0.48±0.23) were significantly lower than in group B (569±278/μl and 0.63±0.34) and A (737±367/4μl and 1.11±0.63).Among immunoglobulins quantified, serum levels of IgG and A were elevated in group C (2364±750mg/dl and 341±220mg/dl and 257±148mg/dl). Particularly, the inverse correlation between OKT4 cells and IgA levels was shown in HIV seropositive patients. The coefficient of correlation in group C (r=-0.341) was stronger than that in group B (r=-0.105). On the other hand, no relationship was found between IgM levels and seropositivity.Elevated serum β2-microglobulin levels were significantly correlated with reduced OKT4 cells in seropositive patients, especially in group C (r=-0.513).Our data suggest that assays of serum IgA, β2-microglobulin and HIV antigen are useful predictors for the condition and prognosis of HIV infection, furthermore the evaluation of therapy.

In vitro B-lymphocyte switch disturbance from IgM into IgG in IgM mesangial nephropathy.

In vitro immunoglobulin (Ig) synthesis using a co-culture technique after activation of lymphocytes with pokeweed mitogen, T-cell subsets and interleukin-2 (IL-2) production was studied in 10 children who suffered from IgM mesangial nephropathy (IgMN), 10 children who suffered from minimal change nephrotic syndrome (MCNS) with hypercellularity and 6 children who suffered from MCNS with normal cellularity during the acute nephrotic phase. Reduced in vitro IgG production was found in the presence of OKT8 cells from all groups of patients. However, in vitro IgM production was increased only in OKT8 cells from IgMN and MCNS patients with hypercellularity. In vitro Tac expression on the OKT8 cells, IL-2 production, T-cell subsets including Leu2a+15+ (suppressor T-cells), Leu2a+DR+ (activated suppressor T-cells) and Leu3a+8+ (suppressor T-cell inducer) were all increased in IgMN and MCNS patients with hypercellularity. There was a significant correlation between in vitro IgM production by co-culture technique and IL-2 production. These results strongly suggest the hyperfunction of isotype-specific suppressor T-cells which may affect the switch of IgM B-cells to IgG B-cells in IgMN and MCNS patients with hypercellularity and may be used to explain in part the clinical findings of lower serum IgG and increased IgM in those patients.

Immunohistochemical detection of tissue-infiltrating lymphocytes in bladder tumors.

Local immunocompetence in patients with bladder tumors was evaluated immunohistochemically using monoclonal antibodies. As well as investigating the subsets of peripheral blood lymphocytes by flow cytometry, the subpopulations of tissue-infiltrating lymphocytes were investigated in frozen specimens from bladder cancers (n = 25) and from noncancerous tissues (n = 4). Six serial sections were stained with Leu4, Leu7, Leu10, LeuM3, OKT4, and OKT8 antibodies, respectively. Marked lymphocytic infiltration into bladder tumors was a favorable prognostic sign. T cell infiltration was marked in the noninvasive group and was prominent around tumor cells, whereas B cells were rare in the stroma. T cells predominated over B cells in 19 of 25 bladder tumors. In patients with low-stage tumors, OKT8 cells were more prominent than OKT4 cells. NK cells accumulated around the cancer cells and infiltrated within cancer nests; NK cell infiltration was scanty in high-stage cases. There was a slight scattering of macrophages in 13 cases. In contrast to the findings in subsets of tissue-infiltrating lymphocytes, subsets of peripheral blood lymphocytes did not correlate with stage of disease. These findings suggest the presence of local immunosurveillance against bladder tumors. To elucidate host immune response against tumor, it may be important to characterize tissue-infiltrating lymphocytes.

Immunological Function in Head-injured Patients

The immunological function of 29 head-injured patients was investigated, with special reference to the relationships between changes in immunity and both severity of head injury and age. The patients were classified according to Glasgow Coma Scale scores (15, 9 to 14, and 3 to 8) and age (under 35, 35 to 65, and over 65 years). T cell subsets (OKT4 and OKT8) and Leu-11a cells were studied by flow cytometry with the use of monoclonal antibody. Lymphocyte stimulation indices were also evaluated. The percentage of OKT4 cells was significantly decreased in the young patients with severe head injury, whereas the percentage of OKT8 cells remained almost within the normal range. Thus, the ratio of OKT4 to OKT8 cells was decreased. The percentage of Leu-11a cells showed no correlation with severity of injury or age. Lymphocyte stimulation indices were reduced in cases of severe head injury. In this study, patients with severe head injury were immunosuppressed, particularly those under age 35.

伝染性単核症におけるＴリンパ球の動態

Infectious mononucleosis due to Epstein-Barr virus (EBV) is an initial viral infection of B lymphocytes usually followed by extensive proliferation of T cells. Functional studies have shown that these T cells are cytotoxic to EBV-infected lymphoid cells and inhibit their proliferation. They also suppress autologous T-cell proliferation.In an attempt to contribute to the understanding of the immunoregulation in infectious mononucleosis, we used monoclonal antibodies to characterize the peripheral lymphoid population in this disease.We found an increase in the total number of T cells and OKT3, OKT8 and OK-Ial positive cells in patients with acute infectious mononucleosis, and concluded that EBV infection triggers the proliferation and activation of T suppressor and/or T cytotoxic cells.

Lymphocytotoxic antibodies in systemic lupus erythematosus: studies of their temperature dependence, binding characteristics, and specificity in vitro.

The lymphocytotoxicity of 33 lupus sera was tested against purified helper/inducer (OKT4) and cytotoxic/suppressor (OKT8) subsets of T lymphocytes at 15 degrees C and 37 degrees C in vitro. There was significantly less killing of both OKT4 and OKT8 cells at 37 degrees C (p less than 0.001 and p less than 0.01) and the ratio of OKT4/OKT8 cell killing at 15 degrees C (1.39 (0.73); mean (SD] was different from that observed at 37 degrees C (0.79 (0.42)) (p less than 0.001). OKT4 killing was greater than OKT8 killing in 21 out of 33 sera at 15 degrees C, while 22 of these sera showed predominantly OKT8 cytotoxicity at 37 degrees C. The relation between the OKT4/OKT8 cell ratio and OKT4/OKT8 serum killing was examined in 22 patients at both temperatures: a significant inverse correlation was observed at 37 degrees C (r = -0.53; p = 0.015) but not at 15 degrees C (p greater than 0.05). The addition of metabolic and cytoskeletal inhibitors increased cytotoxicity at 37 degrees C, but not IgM surface binding. A Scatchard binding analysis of the reaction at 15 degrees C showed that large numbers of antibody molecules were bound to both subsets, with a low average dissociation constant of less than or equal to 6 x 10(-8) mol/l, and electrophoretic blotting indicated that the target surface antigens varied in type and number among individual lymphocytotoxic sera. The demonstration of temperature dependent, tight binding between lymphocytotoxic antibody and variable antigens on the T cell surface emphasises the potential for this phenomenon to affect lymphocyte function in vivo in patients with systemic lupus erythematosus.

Resting metabolic rate of the critically III patient: Measured v predicted : Weissman C, Kemper M, Askanazi J, et al. Anesthesiology 64:673, 1986

Local immunocompetence was evaluated immunohistochemically in patients with bladder tumors before and after local injections of an immunomodulator. The subpopulations of tissue infiltrating lymphocytes (TIL) were examined by staining six serial sections with Leu4, Leu7, LeulO, LeuM3, OKT4, and OKT8 antibodies. T cells predominated over B cells in 19 of 25 bladder tumors. T cell infiltration was prominent around tumor cells, and it was marked in non-invasive tumors. B cells were rare in the stroma. In patients with low-stage tumors, OKT8 cells were more prominent than OKT4 cells. NK cells accumulated within cancer nests but their infiltration was scanty in invasive bladder tumors. Before surgery, immunomodulators (OK-432, IL-2) were injected intratumorally. Their administration resulted in marked increase of T and NK cells, irrespective of the stage of disease; there was a slight increase in B cells. These findings suggest that local immunosurveillance plays a role against bladder tumors. Further studies are required to elucidate host immune responses in the microenvironment of the cancer site, as well as the systemic immune reaction.

EFFECT OF RADICAL MASTECTOMY ON IMMUNE COMPETENT CELLS

In order to appreciate immunodepression following radical mastectomy, number and condition of peripheral lymphocytes were examined.Blood samples were drawn on the preoperative day and on the 3rd, 7th and 14th postoperative days from 11 breast cancer patients. The peripheral lymphocyte subsets (OKT3, OKT4, OKT8 and OK1al positive cells) were determined by flowcytometry using respective monoclonal antibodies. Lymphocyte blastogenesis was evaluated by the ethidium bromide flourescence assey.Lymphocyte numbers were significantly decreased for postoperative 3 days and returned to the preoperative levels by the 7th postoperative day. The ratios in each of the lymphocyte subsets did not show any change throughout the investigation period. The absolute counts of each of OKT3, OKT4 and OKT8 positive cells were significantly decreased for 3 days after operation and returned to the preoperative levels by the 7th postoperative day. The lymphocyte blastogenesis was significantly depressed for 3 days after operation and returned to the preoperative level by the 7th postoperative day.It is considered that the postoperative immune depression is physiological reaction to maintain human homeostasis, however, it is disadvantageous for cancer patients, because of its possible enhancement of metastasis and progress of the disease. Accordingly, it is available to know the immune status of cancer patients for postoperative management.

Lymphocyte Subpopulation Monitoring in Cyclosporine-Treated Patients Following Heart Transplantation

Circulating lymphocyte subpopulations were studied in 18 consecutive patients treated with cyclosporine-prednisone immunosuppression during the first month following heart transplantation. Eleven patients showed no evidence of graft rejection. There were eight episodes of acute rejection demonstrated at endomyocardial biopsy in 7 patients. Three patients were treated with corticosteroids, 3 were treated with rabbit antithymocyte globulin (RATG), and 1 died before treatment (early mortality: 5.6%). Using the monoclonal antibody technique, 150 determinations of lymphocyte subpopulations were performed and were correlated with 72 endomyocardial biopsy specimens. Cyclosporine immunosuppression caused a significant ( p < 0.05) decrease in total lymphocyte count (38%) and in the number of OKT3 (52%) and OKT4 cells (55%). During acute rejection, total lymphocytes and OKT3, OKT4, and OKT8 cells all increased significantly, but the T4 to T8 ratio did not change significantly. Treatment of rejection with corticosteroids resulted in a moderate but not significant decrease in all T-cell types, whereas RATG caused a marked but not selective decrease in all T-cell groups. In conclusion, T cells decrease with cyclosporine immunosuppression and with treatment of rejection and increase at onset of rejection, but the T4 to T8 ratio has no predictive value for the diagnosis and severity of rejection, and the sensitivity of the method does not permit its use to assess the degree of immunosuppression with cyclosporine following heart transplantation.