IL-2 and IL-15 play an important roles in regulating the lymphocyte function and homeostasis. Advances in understanding of the cellular and molecular biology of IL-2 and IL-15 and their receptor complex have provided rationale to better utilize them to expand and activate immune effectors in patients with cancer. These two cytokines stimulate similar responses from lymphocytes in vitro, but play markedly distinct roles in lymphoid biology in vivo. Their distinct physiological functions can be ascribed to distinct signaling pathways initiated by distinct cytokine receptor subunits, differential expression patterns of their receptors. Recently, the discovery of a novel mechanism of IL-15 cytokine signaling, trans-presentation, has provided insights into the divergent ways of these cytokine function. Although their heterotrimeric receptors have two receptor subunits in common, these two cytokines have contrasting roles in adaptive immune responses. The unique role of interleukin 2 is in the elimination of self-reactive T cells to prevent autoimmunity. By contrast, interleukin 15 is dedicated to the prolonged maintenance of memory T-cell responses to pathogens. As discussed in this article, the biology of IL-2 and IL-15 two cytokines will affect the development of novel treatment for malignancies and autoimmune diseases.
Humans ; Immunotherapy ; Interleukin-15 ; immunology ; metabolism ; Interleukin-2 ; immunology ; metabolism

OBJECTIVETo investigate the influence of the LPS of Bacteroides fragilis on the secretion of IL-2 and IL-4 from the peripheral blood mononuclear cells of normal individuals, so as to elucidate the mechanism of the infection by Bacteroides fragilis.

METHODSLPS was obtained from both the strains isolated from patients and from standard NCTC9343. Peripheral blood mononuclear cells (PBMCs) were treated with different concentrations of LPS thus obtained. The supernatants from the cell culture of the PBMCs were harvested at 24 PBHs and were subjected to the determination of the IL-2 and IL-4 contents by ELISA method. RESULTS The IL-2 secretion from the PBMCs of normal volunteers was obviously inhibited by the LPS from Bacteroides fragilis (P < 0.01), and the inhibitory effect was dose-dependent. Nevertheless, the IL-4 secretion from the PBMCs of normal volunteers was significantly stimulated by the LPS from Bacteroides Fragilis (P < 0.05), and it was not concentration dependent. There was no difference between the effects of the LPSs from patients and standard strains (P < 0.05).

CONCLUSIONThe LPS from Bacteroides fragilis was inhibitory to the secretion of IL-2 from PBMCs and was stimulative to that of IL-4 from PBMCs of normal human persons.

Bacteroides fragilis ; metabolism ; Cells, Cultured ; Humans ; Interleukin-2 ; immunology ; secretion ; Interleukin-4 ; immunology ; secretion ; Lipopolysaccharides ; pharmacology ; Monocytes ; drug effects ; immunology

OBJECTIVEAge-related increment of the prevalence of CD4(+)CD25(+) regulatory T (Treg) cells were described controversially, and whether such changes explain immune dysfunction in the elderly is still unclear. The aim of this systematic review is to evaluate the role of the Tregs in immunosenescence.

METHODSMedline and manual searches were performed to identify all published epidemiological and animal studies investigating the efficacy of the association between immunosenescence and Treg cells.

RESULTSIt was founded that the frequency, phenotypic characteristics, and number/function of Tregs were altered significantly with aging. Medical conditions in individuals with advanced ageas well as apoptosis intensity of Treg cells had an impact on the accumulation of Tregs which in turn could deteriorate cytotoxic activity of CD8(+) T and NK cells and production of IL-2. The range of immune cells that could be suppressed by Treg cells was quite wide and covered CD4(+)CD25(+) T cells, NK cells, dendritic cells and even monocytes. These changes were observed both in humans and experimental animals. Besides, it was believed that frequency of Tregs increased with age and was accompanied by intensified suppressive activity for Tregs in patients, for example, with Alzheimer disease (AD) and Parkinson disease (PD). The impaired condition of CD4(+) T cells, so-called immunosenescence, rendered transplant recipients less responsive to an allogeneic kidney graft, an effect that was limited to transplant recipients who were aged over 60 years.

CONCLUSIONSTreg cells are associated with immunosenescence. All these changes contribute to the aging-related decline of immune responses and lead to the higher risk of immune-mediated diseases, cancer or infections in aged individuals.

Aging ; immunology ; Animals ; CD4 Antigens ; immunology ; Humans ; Interleukin-2 Receptor alpha Subunit ; immunology ; T-Lymphocytes, Regulatory ; immunology

OBJECTIVETo investigate the influence of escharectomy during shock stage on systemic and intestinal immune function and its mechanism in scalded rats.

METHODSNinety-six Wistar rats were employed in the study of which 8 were used as normal control group. The donor skin from the trunk in twenty-four rats were preserved in liquid nitrogen. The other 64 rats were subjected to 30% full-thickness scalding, and they were randomly divided into A (n = 24, no treatment after scalding), B (n = 24) and C (n = 16) groups. Physiological saline was intraperitoneally injected (50 ml/kg) on the 24 post-scalding hours to the rats in the B and C groups. The rats in B group underwent escharectomy during shock stage, and the excision wounds were covered with the cryo-preserved alloskin. The rats in C group received the same treatment as in B group but at 72 post-scalding hours. The change in the proliferative ability of splenic lymphocytes, the plasma and intestinal tissue content of interleukin 2 (IL-2), the contents of sIgA in intestinal mucus, and the content of DAO in the intestinal tissue were observed on 2, 4 and 8 post burn days (PBD) in A and B groups and also on 4 and 8 PBD in C group, respectively.

RESULTSThe splenocytic proliferative ability, IL-2 level in the plasma and intestinal tissue, and the sIgA content in intestinal mucus in the rats in A, B and C groups were lower than that in control group at all time points (P < 0.05). The proliferative ability of splenic lymphocytes in B group on 4 and 8 PBD and in C group on 8 PBD respectively was similar to that in control group. Whereas the IL-2 content in plasma and in intestinal tissue was higher in B and C groups than that in A group (P < 0.01). The sIgA content in intestinal mucus in B group was twice of that in C group respectively [(3.51 +/- 2.14) mg/g vs (1.40 +/- 0.64) mg/g, (3.03 +/- 0.95) mg/g vs (1.52 +/- 1.26) mg/g (P < 0.05 or P < 0.01)] on 4 and 8 PBD. The DAO activity in the intestinal tissue in A group was lower than that in control and B group (P < 0.05) on 4 and 8 PBD.

CONCLUSIONEscharectomy during shock stage might be beneficial to the recovery of the systemic and intestinal immune functions in rats with scalding injury.

Animals ; Burns ; immunology ; surgery ; Immunoglobulin A, Secretory ; immunology ; Interleukin-2 ; immunology ; Intestines ; immunology ; Male ; Rats ; Rats, Wistar ; Shock, Traumatic ; immunology ; surgery ; Skin Transplantation ; immunology ; T-Lymphocytes ; immunology

This article reviews that as a functionally and phenotypically distict immunoregulatory T cell subpopulation, CD4(+)CD25(+) regulatory T cells can suppress the activation and proliferation of CD4(+)CD25(-) T cells and CD8(+) T cells and the production of IL-2 and IFN-gamma. These regulatory cells play an important role in allograft tolerance, although the mechanisms are not completely understood to date. CD4(+)CD25(+) regulatory T cells can be isolated, activated and expanded in vitro without loss of their immunoregulatory function. The suppressive function of activated CD4(+)CD25(+) cells is antigen non-specific. Ex vivo activated and expanded regulatory T cells have a perspective for practical use.
CD4 Antigens ; blood ; CD8 Antigens ; blood ; Cell Division ; immunology ; Humans ; Interferon-gamma ; blood ; Interleukin-2 ; blood ; Receptors, Interleukin-2 ; blood ; T-Lymphocytes ; cytology ; immunology ; metabolism ; Transplantation Tolerance ; immunology

Humans ; Interleukin-2 Receptor alpha Subunit ; Liver Diseases ; immunology ; T-Lymphocytes, Regulatory ; immunology

Spontaneous remission (SR) of leukemia is a rare event in clinic, which possibly correlated with severe infection and sepsis, but its exact mechanism has not been confirmed. Plasmacytoid dendritic cells (pDC) and myeloid dendritic cells (mDC) play a key role in innate and adaptive immunity respectively. A patient with severe infection of staphylococcus aureus acquired completely spontaneous remission (SR), moreover a increased number of pDC were observed, suggesting that bacteria-activated pDC may play an important role in SR. This study was purposed to explore if the bacteria can stimulate pDC successfully and get a functional pDC. Both pDC and mDC were isolated from freshly collected, leukocyte-rich buffy coats from healthy blood donor and leukemic patient with SR by using MACS and FACS. The pDC were cultured in RPMI 1640 medium and were stimulated with different kinds of bacteria and the expression of CD40, CD86 and HLA-DR on the cell surface was analyzed by flow cytometry. The cytokine (IFN-α, IL-12, IFN-γ, IL-2, IL-4, IL-10) production was measured by using ELISA kits. The results showed that the stimulation with staphylococcus aureus and pseudomonas aeruginosa resulted in the maturation of pDC, which secrete a large number of IFN-α and promote the differentiation of naive CD4⁺ T cells to Th1 cells. The activated pDC expressed high level of CD40 and CD86 and showed higher T cell stimulatory capacities. It is concluded that staphylococcus aureus and pseudomonas aeruginosa can activate pDC, the activated pDC secrete high quantity of IFN-α. This result suggests that bacteria stimulated pDC may play a key role in SR of leukemia following severe infections.
CD4-Positive T-Lymphocytes ; Dendritic Cells ; immunology ; microbiology ; Humans ; Interferon-alpha ; Interleukin-10 ; Interleukin-12 ; Interleukin-2 ; Interleukin-4 ; Leukemia ; diagnosis ; immunology ; microbiology ; Remission, Spontaneous ; Staphylococcus aureus

Humans ; Interleukin-2 Receptor alpha Subunit ; immunology ; Interleukin-7 Receptor alpha Subunit ; immunology ; Liver Cirrhosis, Biliary ; immunology ; T-Lymphocytes, Regulatory ; immunology

OBJECTIVE: To obtain a global view of lymphocyte subset changes in the peripheral blood and cytokine profile in patients with class IV lupus nephritis (LN). METHODS: A total of 30 patients with biopsy proven active class IV LN, 30 patients with biopsy proven active class V LN, and 30 healthy controls were enrolled. Serum concentration of Th1 cytokines (IFN-γ, IL-1, IL-2, and TNF-α) and Th2 cytokines (IL-4, IL-5, IL-6, IL-10, IL-13) were simultaneously analyzed by Fast Quant Human Th1/Th2 protein array. The expression of lymphocyte subsets was measured by flow cytometer. Clinical parameters such as urine protein of 24 h, autoantibodies and complement were detected. Pearson analysis was used to examine the relation between lymphocyte subsets and clinical parameters, cytokine and clinical parameters. RESULTS: The patients with class IV LN had evident anemia (P<0.001), hypocomplementemia, and hypoalbuminemia (P<0.05). There were no significant difference both in the ratio and number of CD4+ lymphocytes between the controls and the patients. In the patients with class IV LN, the ratio and number of CD4+ lymphocytes were both lower than those of the controls (P<0.01). The ratio and number of CD20+ lymphocytes were both higher than those of the controls (P<0.05), and a significant decrease in CD4+CD25+Foxp3+ regulatory T cells (Tregs) was observed in the patients compared with healthy age-matched controls (P<0.001). The abnormality of lymphocytes in class IV patients was obviously notable, especially in CD4+CD25+Foxp3+ regulatory T cells. In class IV patients, most of the detected cytokines levels were markedly elevated as compared with the controls, including Th2 cytokines INF-γ (P<0.05), IL-2 (P<0.05) and TNF-α (P<0.01), and Th2 cytokines IL-4 (P<0.05), IL-6 (P<0.05), IL-10 (P<0.01) and IL-13 (P<0.01). Only 4 out of 9 cytokines significantly increased in class V patients. In addition to IL-2, all of them belonged to Th2 (IL-4, IL-10 and IL-13) cytokines. There was negative correlation between CD4+CD25+Foxp3+ regulatory cells and urine protein, anti-dsDNA titer or SLEDAI (r=-0.781, -0.746 and -0.646, respectively; P<0.05). There was positive correlation between IL-5 and anti-dsDNA titer (r=0.708, P<0.05), between IL-5 and creatinine (r=0.681, P<0.05), and between IL-10 and SLEDAI (r=0.877, P<0.01). There was also negative correlation between IL-10 and urine protein of 24 h (r=-0.659, P<0.05), between IL-10 and hemoglobin concentration (r=-0.856, P<0.01), and between IL-13 and urine protein of 24 h (r=-0.769, P<0.05). There was little correlation between cytokines and clinical parameters in patients with class V LN. CONCLUSION There is extensive abnormality in lymphocyte subsets and cytokine profile in patients with class IV LN, which may be the mechanism of immunosuppressive agents to treat patients with class IV LN.
Cytokines ; immunology ; Flow Cytometry ; Humans ; Interleukin-1 ; Interleukin-10 ; Interleukin-2 ; Interleukin-4 ; Interleukin-5 ; Interleukin-6 ; Lupus Nephritis ; classification ; immunology ; T-Lymphocytes, Regulatory ; immunology ; Tumor Necrosis Factor-alpha

CD4 Antigens ; immunology ; Humans ; Interleukin-2 Receptor alpha Subunit ; immunology ; T-Lymphocyte Subsets ; immunology ; physiology ; T-Lymphocytes, Regulatory ; physiology