C-21 steroidal glycosides from Dregea sinensis.

Two new C-21 steroidal glycosides, dregeosides D (1) and E (2), were isolated from the roots of Dregea sinensis. The structures of the isolated compounds were elucidated on the basis of 1D and 2D NMR spectra and HR-ESI-MS analysis. Finally, the inhibited effects of the isolated compounds on interleukin 2 receptor were evaluated by enzyme-linked immunosorbent assay.

Fish oil n-3 polyunsaturated fatty acids selectively affect plasma cytokines and decrease illness in Thai schoolchildren: a randomized, double-blind, placebo-controlled intervention trial.

OBJECTIVE: To determine whether very long-chain n-3 polyunsaturated fatty acids (PUFAs) affect illness and selected plasma cytokines in schoolchildren. STUDY DESIGN: Thai schoolchildren aged 9 to 12 years consumed milk containing placebo (soybean) oil (n = 86) or fish oil (n = 94) on 5 days per week for 6 months; the latter provided 200 mg eicosapentaenoic acid plus 1 g docosahexaenoic acid daily. Episodes and duration of illness were recorded, and plasma interleukin (IL)-2 receptor, IL-6, IL-10, and transforming growth factor (TGF)-beta1 concentrations and the fatty acid profile of plasma phosphatidylcholine determined. RESULTS: After intervention, very long-chain n-3 PUFAs were higher in plasma phosphatidylcholine in the fish oil group than in the placebo group (P < .001). The fish oil group showed fewer episodes (P = .014) and shorter duration (P = .024) of illness (mainly upper respiratory tract) than the placebo group. Plasma IL-2 receptor, IL-10, and IL-6 were not affected by either treatment. Plasma TGF-beta1 increased in both groups, but the increase was smaller in the fish oil group, and at the end of supplementation TGF-beta1 concentration was lower in the fish oil group (P < .001). CONCLUSIONS: Very long-chain n-3 PUFAs reduce illness, mainly infections, in healthy Thai schoolchildren.

Immunological evaluation of Lactobacillus casei Zhang: a newly isolated strain from koumiss in Inner Mongolia, China.

BACKGROUND: There is increasing evidence to suggest an immunomodulation function both within the intestines and systemically upon consuming probiotic species. We recently isolated a novel LAB, Lactobacillus caseiZhang (LcZhang) from koumiss. LcZhang exhibited favorable probiotic properties, such as acid resistance, bile resistance, gastrointestinal (GI) colonization ability, etc. In order to examine the immunomodulatory qualities of LcZhang, we administered LcZhang to healthy mice with varying doses of either live or heat-killed LcZhang and measured various parameters of the host immune response. RESULTS: The study was performed in four separate experiments via oral administration of live and heat-killed LcZhang to BALB/c mice for several consecutive days. We investigated the immunomodulating capacity of LcZhang in vivo by analyzing the profile of cytokines, T cell subpopulations, and immunoglobulin concentrations induced in blood serum and intestinal fluid in BALB/c mice. Only live bacteria elicited a wide range of immune responses, which include the increased production of interferon-gamma (IFN-gamma), and depression of tumor necrosis factor-alpha (TNF-alpha) levels. In addition, interleukin-2 (IL-2) and IL-2 receptor gene transcription increased significantly, but the proportion of T cell subsets appeared to be unaffected. We also observed that LcZhang was capable of inducing gut mucosal responses by enhancing the production of secretory Immunoglobulin A (sIgA) as well influencing the systemic immunity via the cytokines released to the circulating blood. CONCLUSION: The present work shows that the dose-dependent administration of LcZhang is capable of influencing immune responses, implying that it may be a valuable strain for probiotic use in humans.

In vitro and in vivo immunomodulating and immunorestorative effects of Astragalus membranaceus.

Astragalus membranaceus is a common traditional Chinese medicinal plant widely used as a tonic to enhance the body's natural defense mechanisms. In this study, bioactive fractions were isolated from the roots of Astragalus membranaceus. One of these fractions, designated as AI, was found to be the most potent with respect to its mitogenicity on murine splenocytes. Effects of AI on both specific and nonspecific immunity in mouse models were examined. Results showed that AI could exhibit mitogenic and co-mitogenic activities on mouse splenocytes, both in vitro and in vivo. Experiments in human cell culture demonstrated that AI was also active on human lymphocytes. It was found that AI was mitogenic to T cell depleted population but virtually inactive on B cell depleted population. Intraperitoneal injection of AI into mice markedly augmented the antibody response to sheep red blood cells. Besides, both the influx of macrophages into the peritoneal cavity and the phagocytic activity of macrophages were found to be enhanced by AI in vivo. On the other hand, AI could significantly increase the interleukin-2 receptor expression on mouse splenocytes in vitro. In terms of immunorestorative activity, it was found that AI could restore the lymphocyte blastogenic response of the older mice to values that are normally found in the younger mice. Moreover, administration of AI in vivo could partially restore the depressed immune functions in tumour-bearing mice and cyclophosphamide-treated mice. Collectively, the results clearly showed that AI could exhibit immunomodulating and immunorestorative effects, both in vitro and in vivo.

Janus kinase 3: a novel target for selective transplant immunosupression.

Existing immunosuppressants inhibit lymphocyte activation and T cell cytokine signal transduction pathways, reducing the rate of acute rejection episodes to < 10%. However, the widespread tissue distribution of their molecular targets engenders pleiotropic toxicities. One strategy to address this problem seeks to identify compounds that selectively inhibit a target restricted in distribution to the lymphoid system. Janus kinase (Jak) 3 is such a molecule; it mediates signal transduction via the gamma common chain of lymphokine surface receptors. Disruption of this lymphoid-restricted enzyme would not be predicted to produce collateral damage in other organ systems. Development of selective Jak3 inhibitors has been difficult due to crossreactivity with its homologue, Jak2. In contrast to all other putative antagonists, which are discussed in detail herein, one Jak3 inhibitor, NC1153, shows at least 40-fold greater selective inhibition for Jak3 than for Jak2, is robustly synergistic with calcineurin antagonists, and, either alone or in combination with cyclosporin, produces no adverse effects in rodents preconditioned to be at heightened risk for nephrotoxicity, bone marrow suppression, or altered lipid metabolism.

Taban-Arshan: immunocorrector in atopic bronchial asthma.

Taban-Arshan extract decreased expression of T-lymphocyte activation markers, normalized T-cell-mediated immunity, and suppressed increased activity of natural killer receptors during culturing with lymphocytes of patients with atopic bronchial asthma. Taban-Arshan extract normalized activation processes in the B-cell immunity and stimulated expression of receptors of activation-induced apoptosis.

[Immune correction in the therapy of patients with prevalent psoriasis with the help of amino acid complex]. / Immunokorrektsiia v terapii bol'nykh rasprostranennym psoriazom s pomoshch'iu aminokislotnogo kompleksa.

In patients with prevalent psoriasis a positive influence amino acid addition (with the standart therapy) on the clinical status of patients and their immune status induces. As a result of this addition use the lesion area diminished, prolongation of remission periods, reduction of the time spent in hospital.

Diaminobiotin and desthiobiotin have biotin-like activities in Jurkat cells.

In mammals, biotin serves as a coenzyme for carboxylases such as propionyl-CoA carboxylase. The expression of genes encoding interleukin-2 (IL-2) and IL-2 receptor (IL-2R)gamma also depends on biotin. Biotin metabolites are structurally similar to biotin, and their concentrations in tissues are quantitatively important. Here, the hypothesis was tested that biotin metabolites can mimic the effects of biotin on gene expression and thus have biotin-like activities. A human T-cell line (Jurkat cells) was used to model effects of biotin and synthetic metabolites (diaminobiotin and desthiobiotin) on the expression of genes encoding IL-2 and IL-2Rgamma. Cells were cultured in biotin-deficient medium (0.025 nmol/L biotin) for 35 d; controls were cultured in medium containing 10 nmol/L biotin. The biotin-deficient medium was supplemented with 10 nmol/L of diaminobiotin, desthiobiotin, biotin or no biotin 24 h before gene expression analyses. Transcriptional activities of genes encoding IL-2 and IL-2Rgamma were increased up to 43% in cells supplemented with diaminobiotin, desthiobiotin or biotin compared with biotin-deficient cells, as judged by luciferase activities after transfection with reporter-gene constructs. These findings are consistent with the hypothesis that diaminobiotin and desthiobiotin mimic the effects of biotin on gene expression and thus have biotin-like activities. Supplementation of cells with diaminobiotin and desthiobiotin did not affect abundances of holocarboxylases and activities of propionyl-CoA carboxylase, suggesting that effects of synthetic biotin metabolites on gene expression are not mediated by carboxylase-dependent pathways. It is not known whether naturally occurring biotin metabolites also have biotin-like activities.

Effect of alpha 2b interferon on inducement of mIL-2R and treatment of HCV in PBMC from patients with chronic viral hepatitis C.

AIM: To study the level of membrane interleukin-2 receptor (mIL-2R) on surface of peripheral blood mononuclear cells (PBMC) and the therapeutic efficacy of alpha 2b interferon on the treatment of HCV-RNA in PBMC of patients with chronic hepatitis C and to compare the negative rates of HCV-RNA in PBMC, HCV-RNA and anti-HCV in serum. METHODS: Before and after treatment of alpha 2b interferon, the level of mIL-2R of patients with chronic hepatitis C was detected by biotin-streptavidin (BSA). The therapeutic group (26 cases) was treated with alpha 2b interferon (3 MU/d) and control therapeutic group (22 cases) was treated with routine drugs (VitC, aspartic acid). The total course of treatment with alpha 2b interferon and routine drug was six months and per course of the treatment was three months. The levels of HCV-RNA in PBMC, HCV-RNA and anti-HCV in serum were detected before and after a course of the treatment. RESULTS: Before and after treatment of alpha 2b interferon and routine drugs, the levels of mIL-2R in silence stage were (3.44+/-0.77) % and (2.95+/-0.72) %, the levels of mIL-2R in inducement stage were (33.62+/-3.95) % and (30.04+/-3.73) %. There was a significant difference between two groups (P<0.01-P<0.05). After treatment of alpha 2b interferon with 3 MU/d for two courses of the treatment, the total negative rates of HCV-RNA in the PBMC and HCV-RNA, anti-HCV in serum were 42.31 % (11/26), 57.69 % (15/26), 65.38 %(17/26) respectively. After the treatment of routine drug, the negative rates of HCV-RNA in PBMC and HCV-RNA, anti-HCV in serum were 13.64 % (3/22), 22.73 % (5/22), 27.27 % (6/22) respectively. There was high significant difference in the group treated with alpha 2b interferon and the group treated with routine drugs (P<0.01-P<0.05). CONCLUSION: The mIL-2R can be induced by alpha 2b interferon during the treatment. The alpha 2b interferon has a definite effect on the treatment of HCV-RNA in PBMC. The curative effect of alpha 2b interferon is better than that of the routine drugs.

Interleukin-2 receptor-gamma -dependent endocytosis depends on biotin in Jurkat cells.

Biotin has been credited with having beneficial effects on immune function despite observations that biotin supplementation causes decreased secretion of interleukin-2. Here this paradox was addressed by determining whether receptor-dependent internalization of interleukin-2 by immune cells depends on biotin. Theoretically, this would be consistent with both decreased net secretion of interleukin-2 by biotin-supplemented cells (causing increased endocytosis) and beneficial effects of biotin on immune function (causing increased receptor signaling). Jurkat cells were cultured in biotin-defined media (25, 250, or 10,000 pM). Secretion of interleukin-2 correlated negatively with biotin supply, but transcriptional activity of the interleukin-2 gene correlated positively with biotin supply, suggesting that decreased secretion of interleukin-2 by biotin-supplemented cells was not caused by decreased gene expression. Expression of the interleukin-2 receptor-gamma gene was greater at 10,000 pM than 25 pM biotin, mediating increased endocytosis of interleukin-2 in biotin-supplemented medium. Inhibition of endocytosis by genistein and overexpression of interleukin-2 receptor-gamma abolished the effect of biotin. These findings suggest that endocytosis of interleukin-2 depends on biotin.

Immunomodulatory effects of RXR rexinoids: modulation of high-affinity IL-2R expression enhances susceptibility to denileukin diftitox.

Rexinoids binding to both the retinoic acid receptor (RAR) and retinoid X receptor (RXR) families of rexinoid receptors have demonstrated clinical activity in hematologic malignancies and have been shown to mediate genes associated with both growth and differentiation. RXR rexinoids have demonstrated efficacy in the treatment of cutaneous T-cell lymphomas, but the mechanism of action is unclear. We explored the immunomodulatory effects of RAR and RXR rexinoids in human T- and B-cell leukemia cells and demonstrated that RXR rexinoids are capable of up-regulating high-affinity interleukin-2 receptor (IL-2R) expression. Exposure to 10(-6) to 10(-10) M bexarotene or Panretin for 48 hours was associated with increased expression of both the p55 and p75 subunits of the IL-2R in T-cell leukemias and p75 in B-cell leukemias. Furthermore, rexinoid exposure enhanced susceptibility of the cells to denileukin diftitox fusion toxin-targeting and -intoxicating cells expressing high-affinity IL-2R. These results suggest a rationale for combining rexinoids with IL-2R-targeted therapies in lymphoid malignancies as well as possibly in autoimmune diseases.

Immunoregulatory and antioxidant performance of alpha-tocopherol and selenium on human lymphocytes.

The role of alpha-tocopherol (alpha-toco) and selenium (Se) on human lymphocyte oxidative stress and T-cells proliferation were studied by flow cytometry. We measured the hydrogen peroxide and glutathione levels in cultured human T-lymphocytes and the proliferation of their subsets: T-helper/inducer, T-suppressor/cytotoxic, and natural killer and interleukin-2 receptors upon stimulation by the mitogens phytohemaglutinin (PHA) and lipopolysaccharide (LPS). The results indicate that early stimulation by mitogens is affected by the glutathione and hydrogen peroxide status of the T-lymphocytes. The addition of 100 microM or 500 microM alpha-toco or 0.5 microM Se alone shows weak antioxidant and immunostimulant properties. When combined, an enhanced antioxidant and immunoregulatory effect was observed. The present findings indicate that alpha-toco and Se have interactive effects as oxygen radical scavengers, thus promoting human lymphocyte response to antigens. This suggests that micronutrient status is an important factor in considering when interpreting the results of in vitro assays of lymphocyte function.

Apoptosis of airway epithelial cells induced by corticosteroids.

Damage to the airway epithelium is one prominent feature of chronic asthma. Corticosteroids induce apoptosis in inflammatory cells, which in part explains their ability to suppress airway inflammation. However, corticosteroid therapy does not necessarily reverse epithelial damage. We hypothesized that corticosteroids may induce airway epithelial cell apoptosis as one potential explanation for persistent damage. We tested this hypothesis in cultured primary central airway epithelial cells and in the cell line 1HAEo(-). Treatment with dexamethasone, beclomethasone, budesonide, or triamcinolone each elicited a time-dependent and concentration-dependent cell death. This cell death was associated with cleavage of nuclear chromatin, mitochondrial depolarization, cytochrome c extrusion, activation of caspase-9, and expression of phosphatidylserine on the outer cell membrane. Inhibitors of caspase activity blocked apoptotic cell death, as did overexpression of the apoptosis regulators Bcl-2 or Bcl-x(L). We demonstrated that CD95 ligation is not essential for the corticosteroid-induced apoptosis in airway epithelial cells. These data demonstrate that corticosteroids induce apoptotic cell death of airway epithelium. This raises the possibility that at least one of the major components of chronic airway damage in asthma, epithelial shedding and denudation, may in part result from a major therapy for the disease.

An antagonist IL-15/Fc protein prevents costimulation blockade-resistant rejection.

IL-15 is a powerful T cell growth factor (TCGF) with particular importance for the maintenance of CD8(+) T cells. Because costimulation blockade does not result in universal tolerance, we hypothesized that "escape" from costimulation blockade might represent a CD8(+) and IL-15/IL-15R(+)-dependent process. For this analysis, we have used an IL-15 mutant/Fcgamma2a protein, a potentially cytolytic protein that is also a high-affinity receptor site specific antagonist for the IL-15Ralpha receptor protein, as a therapeutic agent. The IL-15-related fusion protein was used as monotherapy or in combination with CTLA4/Fc in murine islet allograft models. As monotherapies, CTLA4/Fc and an IL-15 mutant/Fcgamma2a were comparably effective in a semiallogeneic model system, and combined treatment with IL-15 mutant/Fcgamma2a plus CTLA4/Fc produced universal permanent engraftment. In a fully MHC-mismatched strain combination known to be refractory to costimulation blockade treatment, combined treatment with both fusion proteins proved to be highly effective; >70% of recipients were tolerized. The analysis revealed that the IL-15 mutant/Fc treatment confers partial protection from both CD4(+) and CD8(+) T cell graft infiltration. In rejections occurring despite CTLA4/Fc treatment, concomitant treatment with the IL-15 mutant/Fcgamma2a protein blocked a CD8(+) T cell-dominated rejection processes. This protection was linked to a blunted proliferative response of alloreactive T cells as well silencing of CTL-related gene expression events. Hence, we have demonstrated that targeting the IL-15/IL-15R pathway represents a new and potent strategy to prevent costimulation blockade-resistant CD8(+) T cell-driven rejection.

Functional interleukin-4 receptor and interleukin-2 receptor common gamma chain in human gastric carcinoma: a possible mechanism for cytokine-based therapy.

Interleukin (IL)-2 and IL-4 play a critical role in the regulation of the immune response. Yet both of the receptors for these cytokines have been found on nonhematopoietic cells, including human gastric carcinoma cell lines and tissue specimens. IL-4 causes G1 phase cell cycle arrest of gastric carcinoma; the effect directly correlates with the expression of IL-4 receptor (IL-4R) and is seen within 48 hours after treatment. Cells lacking IL-4R are unaffected by IL-4. We examined signal transduction pathways employed by IL-4 that may account for cell cycle arrest of an established human gastric carcinoma cell line, CRL 1739. Western blot analysis was performed on CRL 1739 cultured in the presence of IL-4 (500 U/ml). Cells were lysed, protein extracted, and electroblotted; blots were then probed with murine mono-clonal antibodies to specific intracellular proteins. Western blotting of CRL 1739 with antiphosphotyrosine antibody (4G10) demonstrated multiple (140 kDa and 65 kDa) phosphoproteins seen only in IL-4-treated CRL 1739. Immunoprecipitation and blotting of CRL 1739 with specific secondary antibodies demonstrated that the 140 kDa phosphoprotein was IL-4R", the 65kDa phosphoprotein was IL-2Rgc, the 130 kDa phosphoprotein was Janus kinase (JAK1), and the 116 kDa phosphoprotein was JAK3. Reverse transcription-polymerase chain reaction with specific primers demonstrated that multiple human gastric tumor specimens expressed IL-4R" and IL-2Rgc but did not express the leukocyte marker CD45. These results suggest that human gastric carcinomas may express functional cytokine receptors, including the IL-2Rgc commonly found in association with the lymphocyte IL-2R. These receptors may represent novel targets for directing cytokine-based therapy.

Functional interleukin 4 receptor and interleukin 2 receptor common gamma-chain on human non-small cell lung cancers: novel targets for immune therapy.

OBJECTIVE: The interleukin 4 receptor has been demonstrated on the surface of human non-small cell lung carcinoma cell lines and tumor specimens. Interleukin 4 causes G1-phase cell-cycle arrest of non-small cell lung cancer cell lines expressing the interleukin 4 receptor; the effect directly correlates with the expression of the interleukin 4 receptor and is seen within 48 hours after treatment. We examined signal transduction pathways used by the interleukin 4 receptor that may account for growth arrest of the cell line LUst but had no effect on another non-small cell lung cancer cell line, SK-MES-1. METHODS: Western blot analysis was performed on both LUst and SK-MES-1 cell lines cultured in the presence of interleukin 4 (500 U/mL). Cells were lysed, protein extracted, and electroblotted; blots were then probed with murine monoclonal antibodies to specific intracellular proteins. RESULTS: Western blotting of the cell lines with antiphosphotyrosine antibody (4G10) demonstrated multiple (140 kd, 100-130 kd, and 65 kd) phosphoproteins seen only in the interleukin 4-treated LUst cell line and not observed in the SK-MES-1 cell lines. Immunoprecipitation and blotting of the LUst cell line with specific secondary antibodies demonstrated that the 140-kd phosphoprotein was the interleukin 4 receptor, the 130-kd phosphoprotein was Janus kinase 1, the 116-kd phosphoprotein was Janus kinase 3, and the 65-kd phosphoprotein was the interleukin 2 receptor gamma-chain. Specific binding was not observed in the non-small cell lung cancer cell line SK-MES-1, suggesting that a functional interleukin receptor gamma-chain was not present. Southern blotting with complementary DNA probes to interleukin 2 receptor gamma-chain confirmed the absence of this receptor on cell line SK-MES-1. CONCLUSIONS: These results suggest that non-small cell lung cancer cells may express functional cytokine receptors, including the interleukin 2 receptor gamma-chain commonly found in association with the lymphocyte interleukin 2 receptor. These receptors may be novel targets for directing cytokine-based immune therapy.

Plant alkaloid tetrandrine downregulates protein kinase C-dependent signaling pathway in T cells.

Tetrandrine, a purified traditional Chinese medicinal herb that acts as an immunosuppressant and a Ca2+ channel blocker, has been clinically used to treat patients with arthritis, silicosis and hypertension. Since T cells play a critical role as autoreactive and pathogenic population in autoimmune diseases, in this study, we examined the immunosuppressive effect of tetrandrine on human peripheral blood T cells. We showed that tetrandrine inhibited phorbol 12-myristate 13-acetate (PMA) + ionomycin-induced T cell proliferation, interleukin-2 secretion and the expression of the T cell activation antigen, CD71. Further investigation of the molecular mechanism demonstrated that tetrandrine inhibited the expression of the protein kinase C-dependent interleukin-2 receptor alpha chain and CD69 but not the expression of the Ca2+-dependent CD40 ligand and CD69. Interestingly, when tetrandrine and cyclosporin A were added together, significant synergism in the suppression of T cell activation was observed. Moreover, of the several tetrandrine analogues studied, hernandezine was the most potent inhibitor of protein kinase C signaling events. These results also suggest that the protein kinase C-inhibitory capacity of tetrandrine and its analogues may not be associated with their function as Ca2+ channel blockers. Lastly, we showed that, within therapeutic concentrations, tetrandrine and its analogues could induce cellular apoptosis, which is defective in autoimmune diseases. In conclusion, our findings provide novel information about the molecular mechanism of the immunosuppressive effect of tetrandrine and its analogues in human peripheral blood T cells.

Effect of dietary n-3 fatty acids on interleukin-2 and interleukin-2 receptor alpha expression in activated murine lymphocytes.

Dietary eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) suppress interleukin-2 (IL-2) secretion and impair T-lymphocyte proliferation. To determine the mechanism of action, mice were fed diets containing either safflower oil (control diet enriched in linoleic acid, 18:2n-6), EPA, DHA or arachidonic acid (20:4n-6). Splenic lymphocytes were isolated and concanavalin A-induced kinetics of IL-2 and IL-2 receptor alpha mRNA expression were determined by relative competitive-PCR. EPA and DHA did not affect IL-2 mRNA expression but suppressed IL-2 receptor alpha mRNA levels. These data show, for the first time, the selective effects of dietary EPA and DHA on T-lymphocyte gene expression.

Promotion of interleukin-2 activity as a strategy for 'rejuvenating' geriatric immune function.

The age-related decline in immune capacities is largely attributable to a decrease in the ability of activated T lymphocytes to achieve efficient clonal expansion. This in turn reflects a decrease in the expression of both interleukin-2 and its receptor. Nutritional/hormonal measures which up-regulate such expression may thus have a 'rejuvenatory' impact on geriatric immune function. Such measures may include: subtoxic selenium intakes, which increase the inducibility of interleukin-2 receptor; high-dose vitamin E and possibly chromium, which may counteract the down-regulatory effect of cAMP on interleukin-2 activity; as well as carotenoids and ascorbic acid. Restoring more youthful serum levels of the hormones DHEA and melatonin may also have a positive effect in this regard. In addition to their likely value for boosting geriatric immune defenses, these measures deserve evaluation as adjuvants to cancer immunotherapies and to drug treatments for HIV infection.

Supplementation with selenium augments the functions of natural killer and lymphokine-activated killer cells.

This study examined the effects of dietary (2.0 ppm for 8 wk) and in vitro (1 x 10(-7)M) supplementation with selenium (Se, as sodium selenite) on the activity of spleen natural killer (NK) cells and plastic-adherent lymphokine-activated killer (A-LAK) cells from C57B1/6J male mice. Dietary supplementation with Se resulted in a significant increase in the lytic activity of activated NK cells, and cells from these highly lytic effector cell populations expressed significantly higher numbers of intermediate affinity interleukin-2 receptors (II-2R)/cell. In the presence of high concentrations of II-2 and 1 x 10(-7)M Se, resting populations of spleen NK cells developed into A-LAK cells that had a significantly enhanced ability to proliferate, as indicated by the significantly higher amounts of nuclear 3H-thymidine incorporation, and a significantly augmented cytolytic activity against both NK-sensitive and NK-resistant target cells. Se appears to enhance the lytic activity of activated NK cells and to augment the proliferation, expansion, and lytic activity of A-LAK cells in the presence of high concentrations of II-2 through its ability to enhance the expression of intermediate affinity II-2R on these cells.