Enhancement of human T lymphocyte functions by prothymosin α. I. Augmentation of mixed lymphocyte culture reactions and soluble protein-induced proliferative responses

Baxevanis, Constantin N.; Reclos, George J.; Panneerselvam, C.; Papamichail, Michail

doi:10.1016/0162-3109(88)90054-9

Cited by 34 publications

(21 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…M L R was performed as previously described [11,12]. Briefly, T lymphocytes (2 x 105 cells/well) were cultured with irradiated (3,000 rad) monocytes which served as stimulatory cells.…”

Section: Mixed Lymphocyte Reaction (Mlr)mentioning

confidence: 99%

“…T lymphocytes (94% posi tive with anti-Leu-4-MAb and < 3% positive for sur face immunoglobulin) were isolated after passing M N C through nylon-wool columns [11]. All MAbs were purchased from Becton-Dickinson (Mountain View, C alif., U SA ) and cells were analyzed by indirect immunofluorescence on a FA CScan (Becton-Dickin son) [12],…”

Section: Cell Purificationmentioning

confidence: 99%

“…Mononuclear cells (M N C) were isolated by Ficoll-Hypaque density gradient centrifugation [11]. Monocytes (90% positive with anti-Leu-M l, anti-Leu-M3 and anti-Lcu-M5 monoclonal antibodies (MAbs), and <5% positive with the T-cell-specific anti-Leu-4 M A b were isolated by adherence o f M N C on plastic surfaces that were pretreated with serum [12]. T lymphocytes (94% posi tive with anti-Leu-4-MAb and < 3% positive for sur face immunoglobulin) were isolated after passing M N C through nylon-wool columns [11].…”

Section: Cell Purificationmentioning

confidence: 99%

See 2 more Smart Citations

The Prognostic Significance of Immune Changes in Patients with Renal Cancer and Melanoma Treated with Interferon-α<sub>2b</sub>

Tsavaris¹,

Baxevanis²,

Kosmidis³

et al. 1995

Tumor Biol

View full text Add to dashboard Cite

We evaluated the response rate and the immunorestorative properties of subcutaneously administered in-terferon-α_2b (IFN- α_2b ) in patients with advanced renal cell carcinoma (RCC) and melanoma (MEL) and correlated the immune status with clinical responses. Thirty-five patients with advanced RCC and 12 with MEL were treated with re-combinant IFN- α_2b The dose was increased progressively from 5 × 10⁶ IU the first week to 10 × 10⁶ IU the second week and thereafter 15 × 10⁶ IU subcutaneously. The response rate for RCC patients was as follows: (1) 6 patients achieved partial responses; (2) 9 patients had stable disease, and (3) 20 patients progressed. The response rate for patients with MEL was as follows: (1) 4 patients experienced partial response and (2) 8 patients progressed. In all patients blood was withdrawn prior to IFN treatment and then monthly. T lymphocytes after isolation from peripheral blood were tested for proliferation in the autologous mixed lymphocyte reaction (auto-MLR), and allogeneic mixed lymphocyte reaction (allo-MLR), interleukin-2 production (IL-2prod), expression of IL-2 receptors (IL-2rec) during the allo-MLR, and interleukin-1 production (IL-lprod) by peripheral blood monocytes. Striking increases were demonstrated in all parameters 1 month after treatment with IFN- α_2b. Patients with RCC experiencing a partial response showed a mean increase of 50% in the auto-MLR, 95% in the allo-MLR, 62% IL-2prod, 88% IL-2rec and 76% in IL-lprod. Patients with MEL presenting with a partial response showed a mean increase of 70% in the auto-MLR, 91% in the allo-MLR, 97% IL-2prod, 78% IL-2rec and 118% in the IL-lprod. On the contrary, the nonresponders had a decrease in the examined parameters, and in some, deterioration of the already depressed immunologic functions was observed. Therefore, in nonresponders with RCC the auto-MLR was decreased -23%, the allo-MLR -32%, IL-2prod -28%, IL-2rec -25% and IL-lprod -22%. In nonresponders with MEL the auto-MLR was decreased -22%, the allo-MLR -33%, IL-2prod -29%, IL-2rec -25% and IL-lprod -28%. Administration of IFN- α_2b results in a marked potentiation of deficient cellular immune response in vitro in those patients with RCC and MEL who respond to the treatment. On the contrary, the nonresponders demonstrated a decrease in the examined parameters and in some, deterioration of the already depressed immunologic functions was observed. Administration of IFN- α_2b results in a marked potentiation of deficient cellular immune response in vitro in those patients with RCC or MEL who respond to the treatment. This may have prognostic significance, and certainly more patients are required to be studied for definite conclusions.

show abstract

“…M L R was performed as previously described [11,12]. Briefly, T lymphocytes (2 x 105 cells/well) were cultured with irradiated (3,000 rad) monocytes which served as stimulatory cells.…”

Section: Mixed Lymphocyte Reaction (Mlr)mentioning

confidence: 99%

Section: Cell Purificationmentioning

confidence: 99%

Section: Cell Purificationmentioning

confidence: 99%

See 1 more Smart Citation

The Prognostic Significance of Immune Changes in Patients with Renal Cancer and Melanoma Treated with Interferon-α<sub>2b</sub>

Tsavaris¹,

Baxevanis²,

Kosmidis³

et al. 1995

Tumor Biol

View full text Add to dashboard Cite

show abstract

“…These potentiating effects induced by ProTo~ are more apparent in deficient cellular immune responses such as those in patients with autoimmune diseases [3,4,20] and cancer (manuscript in preparation). Upon analysing the mechanism of action of ProT~ in these in vitro cellular systems, we found that human monocytes after preincubation with ProTo~ (compared to non-treated monocytes) stimulate stronger T lymphocyte 149 proliferation in the mixed-lymphocyte reaction [6], express higher numbers of membrane HLA-DR antigens [7], and present effectively even extremely low amounts of antigen to T cells [6]. Finally, ProTc~ has been shown to increase the production of interleukin-2 and the expression of interleukin-2-specific receptors in antigen-activated T lymphocytes [5].…”

Section: Discussionmentioning

confidence: 98%

“…ProTcz is a powerful immune response modifier. In in vitro studies, it has been demonstrated to potentiate CD4-positive cell proliferative responses to soluble proteins like keyhole limpet haemocyanin and ovalbumin [6], to enhance the human allogeneic and autologous mixed-lymphocyte reaction [3,4,6,7,20] and to increase the expression of major histocompatibility complex class II antigens on human monocytes [7]. These potentiating effects induced by ProTo~ are more apparent in deficient cellular immune responses such as those in patients with autoimmune diseases [3,4,20] and cancer (manuscript in preparation).…”

Section: Discussionmentioning

confidence: 99%

Promotion of murine antitumour activity by prothymosin α treatment: I. Induction of tumoricidal peritoneal cells producing high levels of tumour necrosis factor α

Papanastasiou¹,

Baxevanis²,

Papamichail³

1992

Cancer Immunol Immunother

Self Cite

View full text Add to dashboard Cite

The effect of prothymosin alpha (ProT alpha) on the survival of DBA/2 mice inoculated with syngeneic tumour cells was studied. DBA/2 mice inoculated intraperitoneally (i.p.) with 2 x 10(5) syngeneic leukaemic L1210 cells developed ascites within 8-12 days and died 10-14 days later. Treatment with ProT alpha consistently inhibited the development of ascites in 20% of the treated animals and prolonged the survival of 40%-60% of the animals up to 70 days. The most effective treatment schedule of ProT alpha was 300 ng/mouse given i.p. at 2-day intervals for 3 weeks followed by a rest period of 7 days, prior to tumour cell inoculation. Peritoneal exudate (PE) cells collected from mice treated with the optimal dose of ProT alpha produced, in the absence of exogenous stimulus, six- to eightfold higher levels of tumour necrosis factor alpha (TNF alpha) than PE cells from control mice. Furthermore these cells exhibited cytotoxic activity against several tumour cell lines including the syngeneic L1210, the TNF-insensitive P815 mastocytoma, the human MOLT-4 lymphoblastic leukaemia, as well as the murine TNF-sensitive L929 fibroblast cell line. Kinetic studies revealed that both production of TNF alpha and tumoricidal activity peaked 7 days after the last injection of ProT alpha and were maintained at high levels over a period of 1 month. Injections with 150 ng ProT alpha slightly improved the survival of mice whereas higher (500 ng and 1000 ng) doses of ProT alpha and a wide range of thymosin alpha 1 doses remained without any effect. PE cells collected from these mice produced extremely low levels of TNF alpha and exhibited negligible tumoricidal activity. Our data demonstrate that ProT alpha has a protective effect in vivo against the growth of adoptively transferred tumour cells and suggest that this effect is, at least in part, mediated by ProT alpha-activated PE cells. These cells were demonstrated to produce high levels of TNF alpha in vitro and to exhibit activity against both TNF-sensitive and TNF-resistant cell lines.

show abstract

Prothymosin α restores depressed allogeneic cell‐mediated lympholysis and natural‐killer‐cell activity in patients with cancer

Baxevanis¹,

Reclos²,

Papamichail³

1993

Intl Journal of Cancer

Self Cite

View full text Add to dashboard Cite

Cancer-bearing patients exhibit a variety of profound T-cell abnormalities which include decreased cytotoxic capacity as measured by allogeneic cell-mediated lympholysis (CML), natural-killer (NK) cell activity, and decreased lymphokine production. In patients with advanced solid malignancies, allogeneic CML, tested by a 4-hr 51Cr-release assay, was significantly lower than in a group of normal individuals. If optimal doses of affinity-purified prothymosin alpha (ProT alpha) were present during mixed lymphocyte culture, the CML of cancer patients was increased almost to normal levels. Mixed lymphocyte reaction, tested by tritiated thymidine uptake, was also decreased in these patients and was enhanced to normal levels if ProT alpha was added to the cultures. NK activity was decreased in these patients according to 51Cr-release assays. ProT alpha increased the NK activity up to normal levels. The reduced NK and CML activities in cancer patients were associated with abnormal production of prostaglandin E2 (high) and interleukin-2 (low), which were to a great extent normalized in the presence of ProT alpha. These results demonstrate that ProT alpha is capable of potentiating or fully restoring the deficient cytotoxic effector function of peripheral mononuclear cells (MNC) in patients with advanced malignancies.

show abstract

Enhancement of human T lymphocyte functions by prothymosin α. I. Augmentation of mixed lymphocyte culture reactions and soluble protein-induced proliferative responses

Cited by 34 publications

References 19 publications

The Prognostic Significance of Immune Changes in Patients with Renal Cancer and Melanoma Treated with Interferon-α<sub>2b</sub>

The Prognostic Significance of Immune Changes in Patients with Renal Cancer and Melanoma Treated with Interferon-α<sub>2b</sub>

Promotion of murine antitumour activity by prothymosin α treatment: I. Induction of tumoricidal peritoneal cells producing high levels of tumour necrosis factor α

Prothymosin α restores depressed allogeneic cell‐mediated lympholysis and natural‐killer‐cell activity in patients with cancer

Contact Info

Product

Resources

About

Enhancement of human T lymphocyte functions by prothymosin α. I. Augmentation of mixed lymphocyte culture reactions and soluble protein-induced proliferative responses

Cited by 34 publications

References 19 publications

The Prognostic Significance of Immune Changes in Patients with Renal Cancer and Melanoma Treated with Interferon-&alpha;<sub>2b</sub>

The Prognostic Significance of Immune Changes in Patients with Renal Cancer and Melanoma Treated with Interferon-&alpha;<sub>2b</sub>

Promotion of murine antitumour activity by prothymosin α treatment: I. Induction of tumoricidal peritoneal cells producing high levels of tumour necrosis factor α

Prothymosin α restores depressed allogeneic cell‐mediated lympholysis and natural‐killer‐cell activity in patients with cancer

Contact Info

Product

Resources

About

The Prognostic Significance of Immune Changes in Patients with Renal Cancer and Melanoma Treated with Interferon-α<sub>2b</sub>

The Prognostic Significance of Immune Changes in Patients with Renal Cancer and Melanoma Treated with Interferon-α<sub>2b</sub>