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Results for “Lymphocyte Cooperation”

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PubMed1982

Cell-cell cooperation in lymphocyte colony formation: studies in human allogeneic marrow transplantation.

The pace of restoration of phytohemagglutinin- (PHA) stimulated lymphocyte colony-forming response was investigated in 50 bone marrow transplant (BMT) recipients (49 allogeneic, 1 syngeneic) studied on 86 occasions. On the majority of occasions (28 of 48), patients studied early (3 to 8 wk) after BMT failed to make detectable lymphocyte colonies, whereas patients studied late (greater than 6 mo) after BMT displayed responses comparable to those of healthy adult volunteers. The sequential study of 10 of the 15 patients with positive lymphocyte colony-forming responses early after BMT revealed that this response is short-lived. The results of recipient donor mixing experiments and experiments involving the addition of the lymphokine interleukin 2 (IL 2) to recipient cells indicated that lymphocytes obtained from unresponsive recipients evaluated early after BMT can be driven to colony formation, and suggest that the major limiting component in such subjects is functional T help.

Bone Marrow Transplantation↗
PubMed1983

Effects of aging on cell cooperation and lymphocyte responsiveness to cytokines.

Functional activities and cell cooperation of macrophages (Mphi), T cells, and B cells of young and old Lewis rats were compared. Splenic M phi from young and old rats provided accessory help for T cell mitogenesis and B cell mitogenesis, provided accessory help for generation of PFC, and produced IL 1 equally well as measured in costimulator assays. Splenic T cells of aged Lewis rats, however, were poorly responsive in mitogen assays and did not respond to supplemental IL 2 and antigen with blast transformation and with increased help for B cells to produce PFC. "Old" B cells did not respond in vitro to mitogens with help from M phi and T cells, nor did they respond to B cell helper factor with increased PFC. The data indicate that hyporesponsiveness of the immune system, especially of B cells, in aged rats is due in part to defective reactivity to interleukins and cytokine(s) and to defective cell-cell cooperation.

Aging↗
PubMed1980

Cooperation of murine F T and parental B lymphocytes in rejection of a xenogeneic tumour: adaptive differentiation of B lymphocytes?

The primary humoral immune response to rat Yoshida ascites sarcoma (YAS) grown in mice was used to study thymus-dependent (T) and bone marrow-derived (B) lymphocyte cooperation. It was shown that B6D2F1 T lymphocytes that do not cooperate with parental B lymphocytes enabled parental B lymphocytes from B6 leads to B6D2F1 radiation chimaeras to reject the tumour. However, when the bone marrow cells from B6 leads to B6D2F1 chimaeras were used to reconstitute parental B6 mice, these B6 leads to B6D2F1 leads to B6 mice lost their tolerance to D2 transplantation antigens, and their B lymphocytes were not able to cooperate with B6D2F1 T lymphocytes. In our search for the reasons for the failure of F1 T cells to be effective in parental and P leads to F1 leads to P TIR mice, rejection of F1 T cells was excluded because : (i) immune reactivity in TIR mice was found to be either absent or minimal; (ii) parental TIR mice did not produce any detectable cytotoxic antibodies after an intravenous injection of F1 splenic T cells; and (iii) YAS rejection was not induced at very high doses of F1 T cells. However, in a cell transfer system we were able to demonstrate that injection of spleen cells from parental TIR mice could thwart the successful cooperation of transferred F1 T cells with host B cells. Collectively, these data suggest that the changes of the collaborative potential of parental B cells as achieved in the F1 environment could be ascribed to 'adaptive' differentiation of B lymphocytes. It appears that the differentiation process that has rendered nonsyngeneic chimaeric cells able to cooperate was independent of the exogenous antigen.

Animals↗
PubMed1975

Cell interactions between histoincompatible T and B lymphocytes. VIII. In vivo cooperative responses between lymphocytes are controlled by genes in the K-end of the H-2 complex.

The genetic restrictions for successful carrier-primed T cell and hapten-primed B cell cooperative interactions were established in a totally in vivo double adoptive transfer system. In complementation experiments, we have demonstrated that genes localized in the K-end of the H-2 complex control successful T-B cell cooperative interactions. Thus, DBA/2 KLH-primed T cells cooperated with (C3H times C3H.OH)F1 and (C3H times C3H.OL)F1 DNP-primed B cells to make a secondary response to DNP-KLH, but not with (C3H times C3H.A)F1 DNP-PRImed cells. The presence of foreign histocompatibility determinants on the F1 B cells did not prevent successful physiologic cell cooperation provided the T and B cells shared common cell interaction genes coded for in the K-end of the H-2 complex.

Aminocaproates↗
PubMed1998

Chlorambucil in indolent chronic lymphocytic leukemia. French Cooperative Group on Chronic Lymphocytic Leukemia.

BACKGROUND: To determine whether chlorambucil treatment benefits patients with indolent chronic lymphocytic leukemia (CLL), we conducted two randomized trials in 1535 patients with previously untreated stage A CLL. METHODS: In the first trial, 609 patients were randomly assigned to receive either daily chlorambucil or no treatment; in the second trial, 926 patients were randomly assigned to receive either intermittent chlorambucil plus prednisone or no treatment. Median follow-up for the first and second trials exceeded 11 and 6 years, respectively. The end points were overall survival, response to treatment, and disease progression. RESULTS: Treatment of indolent CLL did not increase survival in either trial. In the treated group, as compared with the untreated group, the relative risk of death was 1.14 (95 percent confidence interval, 0.92 to 1.41; P=0.23) in the first trial and 0.96 (95 percent confidence interval, 0.75 to 1.23; P=0.74) in the second trial, with 76 percent and 69 percent of patients, respectively, having a response to therapy. Although chlorambucil slowed disease progression, there was no effect on overall survival. In the untreated group in the first trial, 49 percent of patients did not have progression to more advanced disease and did not need therapy after follow-up of more than 11 years; however, 27 percent of patients with stage A CLL died of causes related to the disease. CONCLUSIONS: Chlorambucil does not prolong survival in patients with stage A CLL. Since deferring therapy until the disease progresses to stage B or C does not compromise survival, treatment of indolent CLL is unnecessary.

Aged↗
PubMed1989

Long-term results of the CHOP regimen in stage C chronic lymphocytic leukaemia. French Cooperative Group on Chronic Lymphocytic Leukaemia.

This paper reports the results of the third interim analysis of a randomized clinical trial in poor prognosis chronic lymphocytic leukaemia (stage C). From May 1980 to February 1985, 70 stage C patients were randomized between the two polychemotherapies COP and CHOP (COP+doxorubicin). At the reference date of 1 June 1987 used for this analysis, the mean follow-up was 58 months, 46 deaths were observed, 27 in the COP group and 19 in the CHOP group. Overall survival was significantly improved in the CHOP group (P = 0.0005). The 3-year survival rates were 71% in the CHOP group and 28% in the COP group and the median survival times were 62 months in the CHOP group as compared to 22 months in the COP group. This benefit with CHOP was confirmed when adjusting treatment comparison for nine parameters (P = 0.001) and when considering other endpoints than survival, namely 9-month status and stage. This third interim analysis confirms the results of the first interim analysis that led to an early stopping of this clinical trial and clearly indicates the beneficial effect of low doses of doxorubicin in advanced chronic lymphocytic leukaemia.

Aged↗
PubMed1986

Effectiveness of "CHOP" regimen in advanced untreated chronic lymphocytic leukaemia. French Cooperative Group on Chronic Lymphocytic Leukaemia.

This paper gives the first interim results of a randomised clinical trial of several drug regimens for the treatment of chronic lymphocytic leukaemia. Patients were classified as being in stage A, B, or C depending on clinical findings and peripheral blood picture. Good prognosis patients--ie, stage A (n = 455)--were randomised to receive either no treatment or a course of chlorambucil. Intermediate prognosis patients--ie, stage B (n = 224)--received either chlorambucil or the COP regimen (cyclophosphamide, vincristine, and prednisone). Poor prognosis patients--ie, stage C (n = 60)--received either COP or CHOP (COP plus doxorubicin). The first six courses of polychemotherapy were given every month and the other six every 3 months. 93 deaths were recorded at the time of the analysis. Stages A and B patients did not show significant differences in survival rates between treatment groups. In stage C patients 2-year survival rates were 44% with COP and 77% with CHOP (p = 0.0013, one-sided log-rank test). Disease status, as assessed by staging at 9 months, was also better with CHOP than with COP. These results led to the termination of the trial and its replacement by one in which CHOP is given to intermediate prognosis patients.

Aged↗
PubMed1986

Thymic lymphocytes. III. Cooperative phenomenon in the proliferation of thymocytes under Con A stimulation.

In the present paper, the response of thymocytes to Con A is analyzed in terms of a cooperative phenomenon between medullary thymocytes, cortical thymocytes, thymic accessory cells, and interleukin 2. Medullary thymocytes respond spontaneously to Con A and produce IL-2. The addition of exogenously produced IL-2 enhances their proliferation. Small numbers of cortical (PNA+) thymocytes do not respond to Con A, even in the presence of IL-2-containing supernatant. By increasing the number of PNA+ cells per well, sensitivity to Con A and IL-2 appears. This response may be linked either to the increase in a minor PNA+-responding population and/or to the enhanced contamination by medullary thymocytes and macrophages in non-responding PNA+ thymocyte population. In this hypothesis, either the contaminating cells respond by themselves and/or cooperate with PNA+ cells to induce their proliferation. Coculture of non-responding low numbers of PNA+ thymocytes with Con A- and IL-2-containing supernatant in the presence of PNA- cells containing thymic medullary thymocytes and macrophages always produces a higher response than that of each individual population. These results show that a cooperative phenomenon occurs in the cocultures of PNA+ and PNA- thymic cells. We can show using PNA+ and PNA- thymocytes with different Thy 1 alleles, that indeed both PNA+ and populations participate PNA-thymocytes with different Thy 1 alleles, that indeed both PNA+ and PNA- populations participate in the generation of proliferating cells. We can demonstrate, by lysis experiments with monoclonal antibodies and complement that at the end of coculture, most of the proliferating cells are Lyt 1+, and part are Lyt 2+ or L3T4+. We discuss the fact that the phenotype of the cells after activation does not allow us to deduce the phenotype of their precursors. Lysis of Ia+ cells prior to coculture, reduces the level of the proliferative response but does not modify the percentage of cooperation produced by the coculture. Cooperation with medullary mature thymocytes or the presence of active Ia- accessory cells possibly able to convert to Ia expression during coculture experiments may account for these results.

Animals↗
PubMed1990

A randomized clinical trial of chlorambucil versus COP in stage B chronic lymphocytic leukemia. The French Cooperative Group on Chronic Lymphocytic Leukemia.

In 1980, the French Cooperative Group on Chronic Lymphocytic Leukemia started a randomized clinical trial in which intermediate prognosis patients (stage B) received either an indefinite course of chlorambucil (0.1 mg/kg/d) or 12 cycles of the COP regimen (vincristine, cyclophosphamide, and prednisone). We present the results of the third interim analysis based on 291 patients (151 in the chlorambucil group and 140 in the COP group) with a mean follow-up of 53 months at the reference date of June 1, 1987. At this date, 129 deaths were observed, 65 in the chlorambucil group and 64 in the COP group; there was no improvement in overall survival with the COP regimen (P = .44) even after adjusting for both prognostic and imbalanced factors (P = .24). The 3-year and 5-year overall survival rates were, respectively, 69% and 44% in the chlorambucil group as compared with 73% and 43% in the COP group. The median survival times were 58 months in the chlorambucil group and 57 months in the COP group. Moreover, no significant difference was observed between the two treatment groups in terms of either treatment response, 9-month status, time to disease progression to stage C, or causes of death.

Chlorambucil↗
PubMed1982

[Immunotherapy of malignant tumors with subpopulations of T lymphocytes].

During tumor growth specific suppressor cells and non-specific macrophages increase, while helper T cells decrease, preventing the production of an adequate immunological reaction. This immunosuppression can be subdued transferring specific helper cells, that contribute to the production of effector cytotoxic lymphocytes, cooperate with B lymphocytes to produce anti-tumor antibodies, and induce the accumulation of macrophages, lymphocytes, null cells and granulocytes in the tumor zone. The experiments have been done with sarcomas induced in the BN rat by Moloney virus and methylcholanthrene, respectively. It is possible that the experimental model may be applied to human tumors.

Animals↗
PubMed1988

[Immunological profile of Whipple's disease evolving over a period of 17 years].

This report describes an immunological study made on a 58 years old patient with a Whipple disease diagnosed in 1969 and treated with different antibiotics. All attempts to stop the antibiotherapy resulted in reappearance of clinical symptoms. Further, this patient suffered anguillulosis infection in 1954 and this persists despite thiabendazole therapy, as shown by periodical creeping lunear dermatitis (larva currens). Laboratory investigations displayed low IgM levels and lack of cutaneous reactivity to conventional antigenic challenge. In vitro studies on granulocyte and monocyte phagocytic activity did not display any clearcut deficiency. Finally, this patient displayed peripheral lymphopenia and decrease of the T4+ (CD4) lymphocyte subpopulation. The proliferative response of lymphocytes to phytohemagglutinin stimulation (a cellular T-cell function) was drastically decreased in assays performed during the 16 month duration of patient's exploration. This proliferative defect seems to be due to increased PGE2 release (a 3-5 fold increase was demonstrated), resulting in inhibition of interleukin 2 (IL2) synthesis and activity. Further, patient's lymphocyte normally expressed IL2 receptor. When the B lymphocyte dependent humoral response was assayed, normal B lymphocyte differentiation into plasmocytes was found. However the pokeweed mitogen induced proliferative response of B lymphocyte displayed major decrease in four sequential tests. This might be due to a lack of B cell growth factor (BCGF) activity, since this interleukin involved in T lymphocyte, B lymphocyte cooperation was not found in supernatants of patient's cell. Further, interleukin 1 (involved in macrophage lymphocyte cooperation) was normally produced. In conclusion, no deficiency of in vitro phagocytose was demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Differentiation↗