Session II: Immune Regulation of and by NK Cells

The higher prevalence of autoimmune disease among women compared with men suggests that steroids impact immune regulation. To investigate how sex steroids modulate cellular immune function, we conducted a randomized trial in 12 healthy men aged 35–55 yr treated for 28 days with placebo, a GnRH antagonist, acyline to induce medical castration, or acyline plus daily testosterone (T) gel to replace serum T, followed by a 28-day recovery period. Serum hormones were measured weekly and peripheral blood lymphocytes (PBLs) were collected biweekly for analyses of thymus-derived lymphocyte (T cell) subtypes and natural killer (NK) cells. Compared with the other groups and to baseline throughout the drug exposure period, men receiving acyline alone had significant reductions in serum T (near or below castrate levels), dihydrotestosterone, and estradiol ( P < 0.05). Medical castration significantly reduced the percentage of CD4+CD25+ T cells ( P < 0.05), decreased mitogen-induced CD8+ T cell IFN-γ expression, and increased the percentage of NK cells without affecting the ratio of CD4+ to CD8+ T cells and the expression of NK cell-activating receptor NKG2D or homing receptor CXCR1. No changes in immune composition were observed in subjects receiving placebo or acyline with replacement T. These data suggest that T and/or its metabolites may help maintain the physiological balance of autoimmunity and protective immunity by preserving the number of regulatory T cells and the activation of CD8+ T cells. In addition, sex steroids suppress NK cell proliferation. This study supports a complex physiological role for T and/or its metabolites in immune regulation.

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The role of Natural killer (NK) cells as APCs, Cytotoxicity, Immuno-regulatory in Innate and Adaptive immune as Potential Therapeutic and Preventive Target in Infectious Diseases

International Journal of Scientific and Engineering Research ◽

10.14299/ijser.2021.04.09 ◽

2021 ◽

Vol 12 (04) ◽

pp. 415-437

Author(s):

Dr. Zelalem Kiros Bitsue

Keyword(s):

Immune System ◽

Nk Cells ◽

Natural Killer ◽

Host Defense ◽

Immune Regulation ◽

Innate Immune System ◽

Adaptive Immune System ◽

Innate Immune ◽

Adaptive Immune

Natural killer (NK) cells are lymphocytes of the innate immune system that are critical in host defense and immune regulation. They are activated or inhibited through the ligation of germline-encoded receptors and are involved in mediating cytotoxicity, in producing cytokines and in providing co-stimulation to cells of the adaptive immune system.

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Immune regulation: a critical link between NK cells and CTLs

Immunology Today ◽

10.1016/0167-5699(96)80616-5 ◽

1996 ◽

Vol 17 (4) ◽

pp. 174-176 ◽

Cited By ~ 128

Author(s):

Ferdynand J. Kos ◽

Edgar G. Engleman

Keyword(s):

Nk Cells ◽

Immune Regulation ◽

Critical Link

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Impaired NK-mediated regulation of T-cell activity in multiple sclerosis is reconstituted by IL-2 receptor modulation

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1524924113 ◽

2016 ◽

Vol 113 (21) ◽

pp. E2973-E2982 ◽

Cited By ~ 70

Author(s):

Catharina C. Gross ◽

Andreas Schulte-Mecklenbeck ◽

Anna Rünzi ◽

Tanja Kuhlmann ◽

Anita Posevitz-Fejfár ◽

...

Keyword(s):

Multiple Sclerosis ◽

T Cells ◽

T Cell ◽

Nk Cells ◽

Immune Regulation ◽

Nk Cell ◽

Cytolytic Activity ◽

Regulatory Function ◽

Receptor Modulation ◽

Migratory Capacity

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system (CNS) resulting from a breakdown in peripheral immune tolerance. Although a beneficial role of natural killer (NK)-cell immune-regulatory function has been proposed, it still needs to be elucidated whether NK cells are functionally impaired as part of the disease. We observed NK cells in active MS lesions in close proximity to T cells. In accordance with a higher migratory capacity across the blood–brain barrier, CD56bright NK cells represent the major intrathecal NK-cell subset in both MS patients and healthy individuals. Investigating the peripheral blood and cerebrospinal fluid of MS patients treated with natalizumab revealed that transmigration of this subset depends on the α4β1 integrin very late antigen (VLA)-4. Although no MS-related changes in the migratory capacity of NK cells were observed, NK cells derived from patients with MS exhibit a reduced cytolytic activity in response to antigen-activated CD4+ T cells. Defective NK-mediated immune regulation in MS is mainly attributable to a CD4+ T-cell evasion caused by an impaired DNAX accessory molecule (DNAM)-1/CD155 interaction. Both the expression of the activating NK-cell receptor DNAM-1, a genetic alteration consistently found in MS-association studies, and up-regulation of the receptor’s ligand CD155 on CD4+ T cells are reduced in MS. Therapeutic immune modulation of IL-2 receptor restores impaired immune regulation in MS by increasing the proportion of CD155-expressing CD4+ T cells and the cytolytic activity of NK cells.

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