Effect of anti-CD3 antibody on the generation of interleukin-2-activated lymphocytes from tumor tissues of gastrointestinal cancer.

BACKGROUND. The efficiency of anti-CD3 antibody (OKT3) for adoptive immunotherapy using lymphokine-activated killer (LAK) cells generated from tumor-infiltrating lymphocytes (TIL), regional lymph node lymphocytes (RLNL), and peripheral blood lymphocytes (PBL) was investigated. METHODS. TIL, RLNL, and PBL derived from 39 patients with gastrointestinal cancers (16 gastric cancers, 17 colorectal cancers, and 6 esophageal cancers) were cultured for 4 weeks with 200 U/ml of recombinant interleukin-2. To one group, solid-phase 10 micrograms/ml OKT3 was added during the initial culture period (day 2 or 4). Cytotoxicity against K562 cells (NK-like activity) and Daudi cells (LAK activity) and the phenotypes of effector cells generated after culturing for 2-3 weeks were studied. RESULTS. Proliferative responses were significantly increased by OKT3 in each type of effector cell (P less than 0.01); in particular, TIL expanded more by OKT3 than PBL and RLNL (P less than 0.01). The population of CD8+ CD11b- cytotoxic T-cells in OKT3-stimulated groups was significantly larger than that in unstimulated groups (P less than 0.01), whereas no differences were observed with CD4+ cells (helper/inducer T-cells) and CD8+ CD11b+ cells (suppressor T-cells). OKT3 enhanced the NK-like activity of TIL and PBL but did not affect their LAK activity. OKT3 suppressed the NK and LAK activity of RLNL. CONCLUSIONS. OKT3 stimulation did not significantly enhance the LAK activity, but the authors propose that OKT3 could be an effective addition to adoptive immunotherapy using TIL due to an increased proliferation and generation of a large cytotoxic T-cell population.     

Monoclonal antibody-defined T-cell phenotypes and phytohemagglutinin reactivity of E-rosette-forming circulating lymphocytes from untreated chronic myelocytic leukemia patients

T-cell phenotypes, as defined by murine monoclonal antibodies, (OKT3, OKT4, OKT8, OKIa1), and phytohemagglutinin (PHA) reactivity, were evaluated in E-rosette forming cells (T-cells) from 10 untreated chronic myelocytic leukemia patients. The proportion of T4+ cells was lower in patients than in controls (41.6 versus 61.7%, P less than 0.02); whereas the proportion of T8+ cells was similar in patients and controls. The decrease in T4+ cells in CML resulted in a decrease in circulating T4+/T8+ ratio (P less than 0.02). The Ia1+ T-cells were increased in most CML (8 of 9) patients, while control subjects never displayed Ia1+ T-lymphocytes (P less than 0.01). The PHA reactivity of E-rosette forming lymphocytes was significantly impaired in CML patients with respect to controls (P less than 0.02). The presence of Ia antigen on T-cells was positively correlated with the T8+ cell phenotype (P less than 0.001) and inversely correlated with the T4+ (helper) cell phenotype (P less than 0.05). Furthermore, there was a trend towards an inverse correlation between the PHA response and the level of Ia1+ or T8+ cells, there is no correlation between PHA reactivity and T4+ phenotype. The results suggest that the T-lymphocyte population from untreated CML patients is intrinsically abnormal.     

Intracellular cytokine profiles by peripheral blood CD3+ T-cells in patients with classical Hodgkin lymphoma

The intracellular profiles of T helper type 1 (Th1) and T helper type 2 (Th2) T-cell cytokines by peripheral blood (PB) CD3+ T-cells in patients with classical Hodgkin lymphoma (HL) has not been investigated before. The present study examines the cytoplasmic production of interleukin (IL) 2, 4, 10, tumour necrosis factor alpha (TNFalpha), and interferon gamma (IFNgamma) by activated PB CD3+ T-cells and compares them with the profiles observed with normal individuals. We report a significantly lower mean level of intracellular IL2, TNFalpha and IFNgamma at any time post-cell activation in cells isolated from patients with HL compared with the normal control group. In contrast, the mean level of cytoplasmic IL4 was significantly higher in the HL compared with the control group. No significant difference between the two groups was observed with IL10. In the HL patient group, there was a significantly higher percentage of CD3+CD8+ T-cells that synthesised IL4 compared with the CD3+CD4+ subpopulation, no such difference was observed in normal controls. The intensity of IL4 (expressed as relative median fluorescence) was significantly higher in the CD3+CD8+ cells of the patients with HL compared with the CD3+CD4+ sub-population, or with normal CD3+CD8+ cells. In conclusion, there is reduced intracellular IL2, TNFalpha and IFNgamma and increased cytoplasmic IL4 production by activated PB T-cells in patients with HL. The CD3+CD8+ sub-population is responsible for the increased levels of IL4.     

Effects of antiestrogen and progestin on immune functions in breast cancer patients

Several immunologic variables were evaluated in 14 patients with untreated primary breast cancer and 20 postmastectomized patients undergoing tamoxifen (TAM) or high-dose medroxyprogesterone acetate (MPA) treatment. Immunologic evaluation in the peripheral blood included lymphocyte count, definition of T-lymphocyte subsets by monoclonal antibodies (OKT3, OKT11, OKT4, and OKT8), and lymphocyte blastogenic response to phytohemagglutinin (PHA) and Concanavalin A (Con A). Moreover, the in vitro effect of TAM and MPA on the blastogenic response of peripheral lymphocytes from normal female subjects was tested. Primary breast cancer patients did not differ from controls in any of the variables tested. Similarly, the immunologic variables of the group treated with TAM were normal, with the exception of a slight reduction of the OKT4+/OKT8+ ratio. In MPA-treated patients, a reduction of the percentage of OKT4+ cells and a decrease of the OKT4+/OKT8+ ratio were observed. Moreover, response to PHA was reduced sharply. However, the addition of interleukin-2 (IL-2) to the culture medium restored PHA response. Likewise, the in vitro addition of MPA to peripheral blood lymphocytes from normal female subjects resulted in a sharp dose-dependent depression of PHA response while TAM was ineffective completely. The inhibitory effect of MPA was not evident when IL-2 was added simultaneously to the culture medium. These results show that the administration of high-dose MPA may alter immunocompetence as defined by T-lymphocyte subsets and response to mitogens. The latter effect may be related to a diminished production of IL-2. In contrast, TAM does not appear to have a significant immunodepressant action either in vitro or in vivo.     

Immunoregulatory T-lymphocyte functions in patients with small cell lung cancer

The present study was performed to elucidate the differences in immune status between patients with small cell lung cancer (SCLC) and those with non-small cell lung cancer. The study group consisted of 18 patients with SCLC and 15 with non-SCLC. Two healthy volunteers and 13 patients with benign disease were also included in the present study as the non-cancer control. In the non-SCLC group, although not statistically significant, the percentages of both OKT3+ and OKT4+ T-lymphocytes in the peripheral blood lymphocytes (PBL) were slightly decreased, associated with a slight increase in the percentage of OKT8+ T-cells, and a slight decrease in the OKT4+ to OKT8+ T-cell ratio. In contrast, the PBL of the SCLC patients showed significantly lower proliferative responses to phytohemagglutinin and human recombinant interleukin 2 than did the PBL of both the SCLC patients and the noncancer control group. The ability of PBL to produce lymphokines (interleukin 2 and macrophage activating factor) was significantly impaired in the SCLC group but not in the non-SCLC group. These results suggest that suppression of helper T-cell functions and/or potentiation of suppressor T-cell functions should occur in patients with SCLC.     

Effects of PSK on Interleukin-2 Production by Peripheral Lymphocytes of Patients with Advanced Ovarian Carcinoma during Chemotherapy

The effects of PSK on OKT 4/OKT 8 cell ratio, interleukin-2 (IL-2) production and expression of IL-2 receptor were examined in peripheral blood lymphocytes (PBL) from patients with advanced ovarian cancer during the course of chemotherapy. Preoperative levels of OKT 4/OKT 8 cell ratio and IL-2 production in PBL from patients with advanced ovarian cancer were significantly lower than those in cases of benign ovarian tumor. However, the expression of IL-2 receptor did not show any significant difference between ovarian cancer and benign ovarian tumor patients. When a combination chemotherapy of cisplatin, adriamycin and cyclophosphamide was given, the OKT 4/OKT 8 cell ratio was significantly increased with a significant decrease of the absolute number of the OKT 8 cell subset, while the expression of IL-2 receptor and the absolute number of the OKT 4 cell subset remained unchanged. In contrast, the IL-2 production was markedly depressed after the first course of chemotherapy. When PSK was combined with combination chemotherapy, the degree of inhibition of IL-2 production was reduced (though the effect was not statistically significant). If treatment with PSK was initiated after completion of combination chemotherapy, in addition to a significant elevation of OKT 4/OKT 8 cell ratio the depressed IL-2 production was restored to benign control levels. On the other hand, the expression of IL-2 receptor remained unchanged even if PSK was given after completion of chemotherapy.     

Effects of PSK on interleukin-2 production by peripheral lymphocytes of patients with advanced ovarian carcinoma during chemotherapy

The effects of PSK on OKT 4/OKT 8 cell ratio, interleukin-2 (IL-2) production and expression of IL-2 receptor were examined in peripheral blood lymphocytes (PBL) from patients with advanced ovarian cancer during the course of chemotherapy. Preoperative levels of OKT 4/OKT 8 cell ratio and IL-2 production in PBL from patients with advanced ovarian cancer were significantly lower than those in cases of benign ovarian tumor. However, the expression of IL-2 receptor did not show any significant difference between ovarian cancer and benign ovarian tumor patients. When a combination chemotherapy of cisplatin, adriamycin and cyclophosphamide was given, the OKT 4/OKT 8 cell ratio was significantly increased with a significant decrease of the absolute number of the OKT 8 cell subset, while the expression of IL-2 receptor and the absolute number of the OKT 4 cell subset remained unchanged. In contrast, the IL-2 production was markedly depressed after the first course of chemotherapy. When PSK was combined with combination chemotherapy, the degree of inhibition of IL-2 production was reduced (though the effect was not statistically significant). If treatment with PSK was initiated after completion of combination chemotherapy, in addition to a significant elevation of OKT 4/OKT 8 cell ratio the depressed IL-2 production was restored to benign control levels. On the other hand, the expression of IL-2 receptor remained unchanged even if PSK was given after completion of chemotherapy.     

Characterization of two patients with lymphomas of large granular lymphocytes

Two patients with non cutaneous well-differentiated lymphocytic lymphoma with leukemic spread are reported. The large majority of their peripheral blood mononuclear cells (PBMC) formed rosettes with sheep erythrocytes, had receptors for the Fc portion of IgG, and an enzymatic profile of relatively mature T-cells. These cells were morphologically characterized as large granular lymphocytes. Studies with monoclonal antibodies in one of the cases showed an OKT3+, OKT10-, OKT4-, OKT8-, HNK-1-, OKM1+ phenotype, whereas PBMC from the other case were OKT3+, OKT10-, OKT4-, OKT8+, HNK-1+, OKM1-. PBMC from the first patient were able to suppress in vitro B-cell differentiation and were capable of a strong antibody dependent cellular cytotoxicity (ADCC) activity. Natural killer (NK) activity was reduced. Cells from the other patient who was hypogammaglobulinemic, exerted suppressor activity in immunoregulatory assays, and showed ADCC and NK activity. These data support the existence of LGL lymphomas consisting of the proliferation of mature appearing cells capable of functional activity.     

T-lymphocyte subpopulations in B-cell-derived non-Hodgkin's lymphomas and Hodgkin's disease

The authors used E-rosette formation and OKT3 reactivity to determine the percent of T-cells in lymph nodes involved by B-cell non-Hodgkin's lymphomas (B-NHL) and by Hodgkin's disease (HD). The percent of helper and suppressor/cytotoxic T-cells was determined by reactivity with OKT4 and OKT8, respectively. T-cells were also analyzed for two signs of activation: acquisition of Ia antigens and loss of acid a-naphthyl acetate esterase (ANAE) activity. The results were compared with those of lymph nodes exhibiting benign lymphoid hyperplasia (BLH). The percentage of T-cells ranged from 50% to 82%, mean 63 +/- 13%, in 25 cases of BLH, and from 6% to 62%, mean 23 +/- 11%, in 51 cases of B-NHL. The OKT4/T8 ratio was 1.0 to 6.2, mean 3.4 +/- 2.2, in the cases of BLH, and 0.5 to 5.1, mean 2.4 +/- 1.3, in the cases of B-NHL. There was no obvious or significant correlation between the percent of T-cells or the OKT4/T8 ratio and the surface immunoglobulin isotype expressed by the neoplastic B-cells, the morphologic category of B-NHL, or the clinical stage of disease. Activated T-cells were less than or equal to 3% in the cases of BLH and B-NHL. Fifteen lymph nodes involved by HD contained 44% to 96%, mean 74%, E+ (T) cells. Five of these 15 cases contained a significant number of E-OKT3+ cells suggesting that E-rosette formation is not always a reliable T-cell marker in HD. Three other cases contained a large number of E+OKT3- cells. The OKT4/T8 ratio ranged from 0.4 to 21.7, mean 6.7 +/- 5.3, in these cases, representing the most significant T-cell subset imbalances in this series. Large numbers of Ia+E+ and/or E+ANAE- cells, presumably activated T-cells, were present in 7 of these 15 cases of HD. These studies demonstrate the wide variation in the percent of T-cells and in the T-cell subset distribution in lymph nodes exhibiting benign lymphoid hyperplasia and in lymph nodes involved by B-cell-derived non-Hodgkin's lymphomas and Hodgkin's disease.     

OKM1-positive T-cell leukemias. Relationships among morphologic features, phenotype, and functional activities

The morphologic features, phenotype, and functions of OKM1+ leukemic T-cells were studied. The leukemic T-cells in two patients with chronic lymphocytic leukemia (CLL) had specific features of large granular lymphocytes (LGL), and those in two patients with acute lymphocytic leukemia (ALL) had L2 morphologic characteristics. The phenotype of the leukemic cells from one patient with CLL was OKM1+, ER+, OKT3+, OKT4+, OKT8-, OKIa1-, IgGFc receptor (EA gamma)+, Leu-7+, Leu-11b+, and anti-Tac-. The cells had antibody-dependent cell-mediated cytotoxicity (ADCC), but no natural killer (NK) activity. They had a definitive helper effect on pokeweed mitogen-induced normal B-cell differentiation. The leukemic cells from the other patient with CLL were Leu-7-, and Leu-11b-, and lacked both ADCC and NK activity. The leukemic cells in the two patients with ALL were ER+, OKM1+, Leu-7-, and Leu-11-, and did not have any cytotoxicity. One was EA gamma +, and the other was EA gamma -. These findings suggest that OKM1+ leukemic T-cells consist of at least two subgroups: (1) T-cells with the morphologic features of LGL; and (2) those with a lymphoblastic morphologic type. In either case, the phenotype is novel and suggests the emergence of a small, distinct lymphocyte subset.     

Distribution of histocompatibility and leucocyte differentiation antigens in normal human colon and in benign and malignant colonic neoplasms

Monoclonal antibodies (McAbs) directed against the framework determinants of Class I and Class II products of the major histocompatibility complex (MHC) and against leucocyte differentiation antigens were used in an indirect immunoperoxidase technique to study their expression in normal, benign (adenomatous polyps) and malignant disease of the colon. Class I products (detected by the McAb 2A1) were strongly expressed on all cell types in normal and benign tissues but some carcinomas exhibited a heterogenous pattern of epithelial cell staining and 4/15 were completely negative. Class II products (detected by TDR31.1) were strongly expressed on cells (mainly B lymphocytes) within the lamina propria. In carcinomas TDR31.1 staining was mainly interstitial, but in 2/15, DR + epithelial cells were also detected. In normal and benign tissues, leucocytes (reactive with 2D1) found predominantly in the lamina propria, comprised T cells mainly of the helper/inducer (OKT4) subset, DR + cells in approx. equivalent proportion and a few OKM1+ cells mostly of macrophage morphology. Occasional intraepithelial lymphocytes were of cytotoxic/suppressor (OKT8) phenotype. In malignant neoplasms, there was wide inter and intra-tumour variation in the proportion of leucocytes which were heterogeneous with respect to cell type and confined mainly to the stroma. T cells were consistently predominant, but B cells and macrophages were also present. Two neoplasms showed unequivocal evidence of a shift (relative to peripheral blood) in favour of the OKT8+ subset, but in the majority of tumours OKT4+; and OKT8+ cells were present in roughly similar proportions. Natural killer cells (monitored with Leu7, HNK1) were virtually undetectable in both normal and malignant tissues. There were no apparent correlations between the extent and type of leucocyte infiltration, tumour differentiation or expression of MHC products. Some implications for the extrapolation of in vitro data on leucocyte function to the in vivo situation are discussed.     

T-cell chronic lymphocytic leukemia. T-cell function and lymphokine secretion.

The leukemic T-cells of the six patients with T-cell chronic lymphocytic leukemia (T-CLL), four with CD4 and CD45R-positive (CD4+ CD45R*) T-CLL and two with CD8 and CD45R-positive (CD8+ CD45R+) T-CLL phenotype were studied for detailed immunologic phenotypic and functional characteristics. The levels of soluble interleukin-2 receptors were elevated significantly in the serum of all four patients with CD4+ CD45R+ T-CLL. Moreover, the CD4+ CD45R+ T-CLL patients' T-cells, after in vitro stimulation with phytohemagglutinin and concanavalin A, expressed elevated percentages of interleukin-2 receptors on cells and secreted high interleukin-2 activity. The B-cell growth factor (BCGF) activity from three patients with CD4+ CD45R+ T-CLL was enhanced, but B-cell differentiation factor (BCDF) activity of the all T-CLL patients was decreased. Reduced BCGF and BCDF activity of the leukemic T-cells was one possible mechanism of hypogammaglobulinemia detected in two patients with T-CLL. All T-CLL patients' leukemic T-cells had diminished immunoregulatory functional activity in allogeneic mixed lymphocyte reactions. These observations suggest that leukemic T-cells from T-CLL patients have many immunologic functional defects that may be important in their proliferative potential.     

Oral administration of OK-432 (picibanil). (8th report) clinical application: its immunomodulatory effects on the patients with gastrointestinal cancers

A streptococcal preparation, OK-432 at a dose of 5 KE was orally administered to the patients with gastric or colorectal cancer for 7 approximately 14 days before operation, and its immunomodulatory effects on peripheral blood lymphocytes (PBL), regional lymph node lymphocytes (RLNL) and tumor infiltrating lymphocytes (TIL) were assessed. OK-432 treated group included 5 gastric and 6 colorectal cancers, and control group included 6 gastric and 8 colorectal cancers. After oral administration of OK-432 the proportion of Leu 7+ and Leu 11+ cells in PBL increased, and NK cell activity of PBL also was augmented. The proportion of OKT8+ cells increased in PBL and those of OKT3+ cells and OKT8+ cells decreased in RLNL after oral administration of OK-432. The responsiveness of TIL to autologous tumor extracts in the presence of interleukin-2 was enhanced in oral OK-432 group. These results indicate that oral OK-432 affects on NK and T cells and augments the antitumor immunity of the patients with gastrointestinal cancer.     

Humoral immunodeficiency in T-cell chronic lymphocytic leukemia. An immunologic assessment

The humoral antibody immunodeficiency in two patients with T-cell chronic lymphocytic leukemia (T-CLL) appeared to be the result of immunoregulatory abnormalities in the leukemic T-cell populations. Both patients had CD4+ CD45R+ "virgin" or suppressor-inducer T-CLL, but Patient 1 had hypogammaglobulinemia and Patient 2, immunoglobulin (Ig) M hypergammaglobulinemia. Although, CD25+ interleukin-2 (IL-2) receptors were present on leukemic T-cells of both patient, OKT9+ (CD71) transferrin receptors and OKT10 (CD38) activation antigens were found only on Patient 2's cells. Highly elevated amounts of IL-2 was secreted from phytohemagglutinin-stimulated and concanavalin A-stimulated T-cells in both patients. In Patient 1 with hypogammaglobulinemia, immune defects involve T-cells, first an intense suppressor activity on B-cell-induced IgM and IgG synthesis and, second, deficient production of B-cell growth factor (BCGF) and B-cell differentiation factor (BCDF). In Patient 2, highly elevated BCGF and IgM-specific BCDF was secreted by T-cells, a mechanism leading to IgM hypergammaglobulinemia in this patient. These studies stress the importance of BCGF and BCDF activity of leukemic T-cells in humoral antibody immunodeficiency disorders in T-CLL cases.     

T-cell subsets defined by monoclonal antibodies in monoclonal gammopathy of undetermined significance (MGUS)

Peripheral T lymphocytes from 31 patients with monoclonal gammopathy of undetermined significance (MGUS), and from a group of controls of the same age range, were stained using monoclonal antibodies of the OKT series. The absolute number and the percentage of OKT3+ cells did not differ in patients compared with the controls. The percentage and absolute number of T-cell subsets with helper/inducer OKT4+ and suppressor/cytotoxic OKT8+ phenotype were not different from those of the controls, thus the OKT4/OKT8 ratio in the patients with MGUS was normal (1.60 versus 1.57 in normal controls). These results suggest that MGUS is a B-cell disorder without imbalance of peripheral T-cell subsets unlike B-cell malignancies such as multiple myeloma and B-cell chronic lymphocytic leukemia.     

Changes in peripheral lymphocyte subsets during radiotherapy for lung cancer patients

In order to better understand the immunologic effects of irradiation, blood levels of lymphocyte subsets were sequentially monitored in 37 patients before and during irradiation treatment for lung cancer. During irradiation, the peripheral blood levels of each T cell subgroup, OKT3-reactive (OKT3+), OKT4+, OKT8+ and OKT11+ lymphocytes showed similar radiosensitivity. No selective depletion of either OKT4+ or OKT8+ lymphocytes was seen. The levels of OKT6+ and OKT9+ lymphocytes were different depending on the case. At the end of irradiation, the percent of lymphocytes bearing the OKT10 antigen increased significantly. As to OKM1+ and OKIa1+ lymphocytes, the levels were almost consistent but showed a rather big standard deviation.     

Lymphokine-activated killer activity in long-term cultures with anti-CD3 plus interleukin 2: identification and isolation of effector subsets

Peripheral blood lymphocytes cultured in recombinant interleukin 2 during 3 to 5 days (short-term cultures) develop the ability to lyse natural killer-resistant tumor lines and fresh tumor cells, i.e., express lymphokine-activated killer (LAK) function. Phenotypic analysis has shown these cells to be natural killer cells, i.e., CD16+ and/or Leu 19+ cells. CD3+,CD16- T-cells, instead, develop very low LAK function in these cultures. We recently reported the development of long-term (up to 21 days) cultured cells with LAK activity by stimulation with OKT3 + interleukin 2(IL2). These culture conditions repeatedly resulted in a several hundred-fold expansion in cell number. Specific LAK activity on Day 14 of culture was comparable to that of 3-day LAK cultures and could be further enhanced by the addition of interleukin 1 beta, beta-, or gamma-interferon. Total LAK activity was greatly increased in OKT3 + IL2 cultures over that found in short-term cultures. Isolation of effectors mediating LAK function in long-term cultures stimulated with OKT3 + IL2 showed that both CD3+,CD16- cells and CD16+,CD3- cells tested on Day 14 of culture expressed equivalent levels of LAK activity as shown by lysis of natural killer-resistant targets, HL60 and Daudi. Further dissection of the subpopulations developing LAK activity demonstrated that, in addition to CD16+,CD3- cells, CD3+, CD4-,CD8- cells and Leu 19+,CD3-,CD16- cells also developed high LAK activity in long-term cultures with OKT3 + IL2. Further, long-term culture with OKT3 + IL2 induced increases in the numbers not only of CD3+,CD4-,CD8- cells but also of CD16+,CD3- and Leu 19+,CD3-,CD16- cells. Although there is a significant increase in the number of CD3+,CD8+ cells, neither these, nor the CD3+,CD4+ cells, mediate LAK activity to the same extent as the populations mentioned above.     

卵巢恶性肿瘤患者细胞免疫状免疫状态的研究及临床价值：COKT McAb...

Blood samples from 79 subjects (27 cases of ovarian malignancy, 2 ovarian borderline epithelial tumor, 38 benign gynecologic disease and 12 healthy women) were measured for peripheral blood T-cell subsets using monoclonal antibodies and SPA-Ig rosette technique. It was found that in patients with ovarian malignancy, the percentage of OKT4+ cells was significantly reduced whereas the percentage of OKT8+ cells was markedly increased as compared with those in the healthy women and patients with benign gynecologic disease; OKT4/OKT8 ratio declined obviously; which were more pronounced in patients with advanced or recurrent tumor.     

Inflammatory BAL-fluid and serum parameters in HLA DR17 positive vs. DR17 negative patients with pulmonary sarcoidosis

BACKGROUND AND AIM OF THE WORK: We have previously shown that HLA DR17 is associated with a favourable prognosis in Scandinavian sarcoidosis patients. By studying inflammatory parameters in these patients we wished to increase the knowledge of the involved mechanisms that may underlie good prognosis. METHODS: BAL was performed in 118 sarcoidosis patients, 67 HLA DR17 positive and 51 DR17 negative. BAL cell profile was analysed. The CD4 and CD8 lymphocyte phenotype was determined by flow cytometry. BALF-albumin, BALF-fibronectin (FN) and BALF-procollagen III aminoterminal peptide (PIIINP) were analysed by nephelometric, ELISA and RIA methods respectively. Neopterin and soluble interleukin-2 receptor (sIL2R) in serum were also determined by ELISA. Angiotensin-converting enzyme (ACE) in serum was analysed by spectrophotometry. RESULTS: In DR17+ patients, BAL lymphocytes and eosinophils were significantly decreased (median 30.2 and 0.19 x10(6)/L) compared to DR17- (median 50.2 and 0.64 x 10(6)/L respectively). However the BAL CD4/CD8 ratio was increased in the DR17+ group compared to DR17- (6.2 vs. 4.3). BALF-albumin, FN and PIIINP did not differ between the groups. Serum parameters were decreased in DR17+ patients compared to DR17- (ACE median 28.7 vs. 35.1 U/L, neopterin 9.1 vs. 12.7 nmol/L and sIL2R 296 vs. 605 U/L). CONCLUSIONS: The study revealed that an increased BAL CD4/CD8 ratio, in contrast to BAL lymphocytosis, was seen in a subgroup of sarcoidosis patients earlier associated with a favourable prognosis. Our results support that an increased BAL CD4/CD8 ratio is a favourable parameter in sarcoidosis. The lower ACE activity in the DR 17+ group indicates a reduced granuloma burden in this patient subgroup.     

Correlation between CD4+CD25+Treg Cells and CCR4 in Nasopharyngeal Carcinoma

OBJECTIVE CD4+CD25+ T regulatory (Treg) cells are a population of T cells which suppress an overactive immune system. CCR4 is a chemokine receptor involved in the recruitment of lymphocytes. Nasopharyngeal carcinoma (NPC) is resistant to immunosurveillance, owing to the increased number of tumor-infiltrating Treg cells which are recruited to the tumor by CCR4.METHODS The percentage of CD4+CD25+Treg cells and CCR4+ cells in tissue or peripheral blood (PB) lymphocytes of patients with untreated NPC or normal subjects was analysed by flow cytometry. RESULTS In both tissue and PB lymphocytes, the percentage of CD4+CD25+ Treg cells and CCR4+ cells was significantly elevated in patients with NPC in comparison with that in the normal tissue of controls. Furthermore, in the patients with NPC, a higher percentage of CD4+CD25+ Treg cells was found in the tumor-infiltrating (T1) lymphocyte population than in the PB population. In the NPC patient group, a general trend towards an increased percentage of Tl Treg cells was found in the patients with advanced stage NPC. The number of CD4+CD25+ Treg cells was positively related to the number of CCR4+ cells in the tumor and in the PB of the patients with NPC, while the number of CD4+CD25+ Treg cells was negatively related to the number of CD4+CD25- T cells.CONCLUSION Immunosuppression was observed in NPC, especially at the tumor sites. CD4+CD25+ Treg cells may suppress CD4+CD25- T cells. CCR4 may have an important role in the recruitment of CD4+CD25+ Treg cells to tumor sites, thus causing resistance to immunosurveillance.