Diminution of inducible lymphokine-activated killer cell activity in individuals with AIDS-related disorders

Gryllis, Chryssa; Wainberg, Mark A.; Gornitsky, Mervyn; Brenner, Bluma G.

doi:10.1097/00002030-199012000-00004

Cited by 17 publications

(17 citation statements)

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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: 95%

“…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: 95%

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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“…Infection with human immunodeficiency virus (HIV) type 1 is associated with suppression of non-major histocompatibility complex (MHC) restricted cytotoxicity [2][3][4][5][6][7][8][9][10][11][12][13][14][15]. This suppression is primarily due to a qualitative defect in the NK and LAK cells and is an early manifestation of HIV infection [2].…”

Section: Introductionmentioning

confidence: 99%

Clinical Progression of HIV Infection: Role of NK Cells

et al. 1997

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Bruunsgaard H, Pedersen C, Skinhøj P, Pedersen BK. Clinical Progression of HIV Infection: Role of NK Cells. Scand J Immunol 1997;46:91-95 The purpose of the study was to examine how immune parameters related to non-major histocompatibility complex (MHC) restricted cytotoxicity changed with respect to progression and duration of human immunodeficiency virus (HIV) infection. Forty-one HIV seropositive subjects with a known time for seroconversion were included. The major finding was that a low percentage and number of natural killer (NK) cells were found in the group who had a rapid progression to acquired immune deficiency syndrome (AIDS) (less than 70 months following seroconversion) compared with those progressing more slowly to AIDS (more than 70 months following seroconversion). Furthermore, a significant correlation was found between the number of months from seroconversion to the diagnosis of AIDS and percentages of CD16þ cells (r s ¼ 0.811, P < 0.01), CD56þ cells (r s ¼ 0.647, P < 0.05), and CD16þCD56þ cells (r s ¼ 0.839, P < 0.01) as well as the concentration of CD16þCD56þ cells in the blood (r s ¼ 0.699, P < 0.05). No differences were found in percentages and concentrations of NK cell subsets between subjects with a long history (more than 6 years) versus a short history (less than 6 years) of HIV infection without AIDS. Furthermore, no negative correlations were found between the concentration of any NK subsets and the number of months since seroconversion in HIV seropositive individuals without AIDS. The total concentration of CD16þ, CD56þ, and CD16þ CD56þ cells was lower in the group of HIV seropositive subjects compared with HIV seronegative subjects (age and sex matched), and the concentration of CD16þ cells was lower in those with AIDS than in those without AIDS. In conclusion, low concentration of NK cells in the blood was associated with a more rapid disease progression, indicating that defective non-MHC restricted cytotoxicity may be associated with HIV disease progression.

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“…Recent investigations in our laboratory have demonstrated that asymptomatic seropositive donors can develop cytotoxic LAK cells against K562. Raji, and U-937 targets, and that these LAK cell responses diminish upon disease progression [9,23,24] Importantly, LAK cells derived from asymptomatic HIV-1 individuals have been shown to demonstrate significantly elev;ited cytotoxic responses to HlV-l-infected targets relative to uninfected counterparts [24], This preferential HI V-1-directed target cell response v\;is absent in healthy seronegative eontrols [24].…”

Section: Introductionmentioning

confidence: 99%

Changes in natural immunity during the course of HIV-1 infection

Brenner

Gryllis

Gornitsky

et al. 1993

Clinical and Experimental Immunology

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SUMMARY The role of natural killer (NK) and lymphokine‐activated killer (LAK) cell‐mediated cytotoxiciry in AIDS has yet to be established. The objective of this study was to determine inducible LAK cell responses at different stages of HIV‐1 infection, and specifically to establish the participation of CD8 lymphocytes in these responses. Peripheral blood lymphocytes (PBL) were isolated from healthy seronegative (CDC‐0) subjects and HIV‐1 individuals who were clinically asymptomatic (Centre for Disease Control group 2, CDC‐2) or symptomatic (CDC‐4) with regard to secondary opportunistic infection (OI). LAK cells were generated upon incubation of PBL with IL‐2 and their cytolysis of K562 and U‐937 targets was determined using chromium release assays. The role of CD8+ lymphocytes as progenitors and effectors of these LAK cell responses was determined by immunomagnetic depletion of CD8+ cells from precursor PBL and LAK cells, respectively. LAK cell‐mediated cytotoxicities in HIV‐1‐infected individuals were reduced compared with scronegativc controls without any corresponding changes in the relative proportions of CD56+ (NK) cells among groups. Depletions of CD8+ subsets from either PBL or LAK cells dramatically reduced total LAK cytotoxic responses and LAK activities per unit CD56+ cell in the OI‐CDC‐2 scropositive population. No corresponding changes in LAK activities in seronegative control or HIV+/OI+ CDC‐4 groups were observed. Levels of LAK activity against K562 targets in CDC‐0/HIV and CDC‐4/HIV+ groups correlated with the percentage of CD56+ LAK cells; corresponding LAK activity in the CDC‐2/HIV+ group correlated with the percentage of both CD56+ and CD8+ subsets. These findings suggest that adaptive changes in non‐MHC restricted cytotoxic responses occur in HIV‐1 individuals at early stages post‐HIV infection, before the onset of opportunistic infection.

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Diminution of inducible lymphokine-activated killer cell activity in individuals with AIDS-related disorders

Cited by 17 publications

References 0 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

Clinical Progression of HIV Infection: Role of NK Cells

Changes in natural immunity during the course of HIV-1 infection

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