Human Recombinant Interleukin-2 Partly Reconstitutes Deficient in-Vitro Immune Responses of Lymphocytes From Patients With Aids

Lifson, JD; Mark, D. Humphries; Benike, Claudia; Koths, Kirston; Engleman, E G

doi:10.1016/s0140-6736(84)92220-7

Cited by 78 publications

(28 citation statements)

References 22 publications

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“…In addition, we have shown that cytokine activation of PBMCs taken from these patients generally results in levels of lysis at least as high as the baseline, unactivated NK activity of healthy individuals. Although these findings corroborate those of other investigators [4][5][6][7][8][9][10][11][14][15][16][17], they differ from prior studies in that all of our patients had very low CD4 cells (under 100/mm 3 ). Thus, even the Cytotoxicity was measured in a 4 h 51 Cr-release assay using K562 cells as targets.…”

Section: Discussionsupporting

confidence: 85%

“…As shown by others [4][5][6][7][8][9][10][11][14][15][16][17], IL-2 alone can increase the cytotoxicity of PBMCs from AIDS patients. We have shown that the addition of gamma IFN resulted in a slight increase in cytotoxicity in patients' cells and a statistically significant increase in controls' cells.…”

Section: Discussionmentioning

confidence: 96%

“…Lymphokine activation of PBMCs from HIV-infected patients results in increased cytolytic activity [4,[8][9][10][11]. Although the lymphokine-activated killer (LAK) cells of AIDS patients may not attain the level of cytotoxicity that can be generated from healthy individuals [4,8,9], the ability to increase cytotoxicity suggests that cytokine therapy might have therapeutic value during HIV infection.…”

Section: Introductionmentioning

confidence: 99%

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Lymphokine‐Activated Cytotoxicity in Peripheral Blood Mononuclear Cells of Severely Immunocompromised HIV‐Infected Patients

Forthal¹,

Landucci²,

Robinson

1997

Scand J Immunol

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Forthal DN, Landucci G, Robinson Jr WE. Lymphokine-Activated Cytotoxicity in Peripheral Blood Mononuclear Cells of Severely Immunocompromised HIV-Infected Patients. Scand J Immunol 1997;45:91-95 The authors determined the natural killer (NK) and lymphokine-activated killer (LAK) activities of peripheral blood mononuclear cells (PBMCs) from a severely immunocompromised (CD4 cell counts < 100/mm 3 ) group of AIDS patients, using K562 and U937 target cells. An increase in cytotoxicity was observed in the PBMCs of all 17 patients following a 48 h incubation with the combination of 400 U/ml of recombinant gamma interferon plus 20 U/ml of natural interleukin-2. Although NK and LAK activities were significantly higher in healthy controls than in patients, patients' LAK activity was higher than the NK activity of controls. The authors also demonstrated that the use of medium containing fetal bovine serum, when compared with medium containing autologous serum, increases NK activity without affecting LAK activity. Lymphokine augmentation of cytotoxicity is achievable in severely immunocompromised AIDS patients and might be of benefit in delaying opportunistic infections and malignancies. Donald N.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

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Lymphokine‐Activated Cytotoxicity in Peripheral Blood Mononuclear Cells of Severely Immunocompromised HIV‐Infected Patients

Forthal¹,

Landucci²,

Robinson

1997

Scand J Immunol

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“…Approximately half of the CD 1I+ lymphocytes co-express the CD2 antigen or sheep erythrocyte receptor (23,24). Therefore, previous studies demonstrating IL-2-induced proliferative activity in both erythrocyte-positive and erythrocyte-negative fractions would not be unexpected, and probably does not reflect T cell proliferation (6,7). As approximately one-third of CD 1 + lymphocytes also express the CD8 antigen, the reported proliferation of both CD8+ and CD8-lymphocytes is again consistent with our findings (9, 1 1).…”

Section: Discussionmentioning

confidence: 85%

Lymphocytes expressing type 3 complement receptors proliferate in response to interleukin 2 and are the precursors of lymphokine-activated killer cells.

Gray¹,

Horwitz²

1988

J. Clin. Invest.

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In the absence of antigenic or mitogenic stimulation, certain peripheral blood lymphocytes exhibit proliferative and lymphokine-activated killer (LAK) cell activities when cultured with recombinant IL-2. Both activities were found to be an exclusive property of lymphocytes expressing type 3 complement receptors (CR3) identified by anti-CD1 1 monoclonal antibodies. CD11+ lymphocytes were then fractionated into three subsets by two-color flow cytometry. These included CD16+ cells, which display distinctive Fc receptors for IgG (CD16). Using anti-CD5, the CD11+ CD16-lymphocytes were separated into non-T cell and T cell subsets. The two non-T cell subsets (CD11+ CD16+ and CD11+ CD16-CD5-), but not the T cell subset (CD11+ CD16-CD5+), could proliferate in response to IL-2. Both CD11+ non-T cell subsets, but not the CD11+ T cell subset, had the capacity to mediate natural killer cell activity. However, all three CD1 1 + lymphocyte subsets were capable of generating LAK activity. These findings are consistent with the concept that two signals are required to stimulate T cells to proliferate. However, at least a small subset of blood T cells can be activated by IL-2 to become LAK cells.

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“…Early experiments studying proliferation or IL-2 production from cells of HIV-infected patients stimulated with PHA or tetanus raised the issue of whether a qualitative defect of 1L-2 production existed in these patients (17)(18)(19)(20)(21)(22)(23)(24). The data in Table 2 (Experiment 2), show that IL-2 pro- TET 0 70 180 12 0 0 140 ND 600 PHA 600 500 515 600 250 175 410 400 TET 0 30 120 7 0 0 70 ND HIV PHA 275 375 635 500 10 60 470 200 TET 22 70 280 45 0 10 duction was often higher from PBMCs and CD4 + T cells in response to PHA in HIV + individuals compared to HIV-controls.…”

Section: Il-12 Significantly Increases Il-2 Production From Phastimulmentioning

confidence: 99%

Cytokine interactions in human immunodeficiency virus-infected individuals: roles of interleukin (IL)-2, IL-12, and IL-15.

Seder

Grabstein

Berzofsky

et al. 1995

The Journal of Experimental Medicine

109

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SummaryCytokines have been shown to be powerful regulators of the immune response. In this study, we analyze the effect that the newly recognized cytokine interleukin (IL)-15 has on proliferation and cytokine induction using peripheral blood mononuclear cells (PBMCs) and purified CD4 § T cells from patients infected with human immunodeficiency virus (HIV) who are at various stages in their disease. We observed that IL-15 enhances the proliferative response in a dose-dependent manner from PBMCs of HIV-infected individuals when stimulated by polyclonal mitogen, tetanus toxoid, or HIV-specific antigen. The effects of exogenous IL-15 are substantially diminished by adding a neutralizing antibody to the [3 chain of the IL-2 receptor. Moreover, the ability of IL-15 to increase proliferation is enhanced by the presence of endogenous IL-2 produced in the cultures. The effect that exogenous IL-15 had on IL-2, IL-4, and interferon (IFN)-y induction from PBMC's or CD4 + T cells in response to mitogen or tetanus toxoid was also examined. This was compared to the effect that exogenous IL-2 and IL-12 had under the same conditions. Addition of IL-2 or IL-15 to short-term in vitro cultures of either PBMCs or CD4 + T cells had little effect on IL-2, IL-4, or IFN-~/production. By contrast, IL-12 caused substantial enhancement of both IL-2 and IFN-',/ production from these cultures. The role that endogenous cytokines have on IFN-y induction was also studied. Addition of a neutralizing antibody to the cx chain of the IL-2 receptor or IL-12 to antigen stimulated cultures caused a striking decrease in IFN-y production. Neutralization of endogenous IL-15 also resulted in diminished IFN-y production from cultures stimulated with mitogen. IL-4 and IFN-~/protein production by PBMCs and CD4 + T cells stimulated with mitogen was assessed to see if we could detect a specific bias of cytokine production. Small amounts oflL-4 were detected from CD4 + T cells but not PBMCs from most individuals tested. IFN-y and IL-2, however, were also produced from these same cultures. These results further elucidate the mechanism ofcytokine regulation in HIV-infected individuals, and they provide evidence that IL-15 may be a useful immune modulator.

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Human Recombinant Interleukin-2 Partly Reconstitutes Deficient in-Vitro Immune Responses of Lymphocytes From Patients With Aids

Cited by 78 publications

References 22 publications

Lymphokine‐Activated Cytotoxicity in Peripheral Blood Mononuclear Cells of Severely Immunocompromised HIV‐Infected Patients

Lymphokine‐Activated Cytotoxicity in Peripheral Blood Mononuclear Cells of Severely Immunocompromised HIV‐Infected Patients

Lymphocytes expressing type 3 complement receptors proliferate in response to interleukin 2 and are the precursors of lymphokine-activated killer cells.

Cytokine interactions in human immunodeficiency virus-infected individuals: roles of interleukin (IL)-2, IL-12, and IL-15.

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