Clinical relapses of multiple sclerosis are associated with ‘novel’ valleys in natural killer cell functional activity

Kastrukoff, Lorne F.; Lau, Anthony; Wee, Richard; Zecchini, Daniel; White, Richard Allen; Paty, Donald W.

doi:10.1016/j.jneuroim.2003.10.001

Cited by 80 publications

(68 citation statements)

References 36 publications

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“…We were not able to explore whether DC are involved in NK-mediated death of autoreactive cells because DC are required for PLP responses during the induction of EAE. The results of our experiments are in line with an interesting observation on the regulatory role of NK cells in EAE and MS (52)(53)(54)(55) which demonstrated that high levels of activated NK cells correlated with lower reactivity to myelin basic protein.…”

Section: Discussionsupporting

confidence: 89%

Brain-Derived Heat Shock Protein 70-Peptide Complexes Induce NK Cell-Dependent Tolerance to Experimental Autoimmune Encephalomyelitis

Gałązka

Stasiołek

Walczak

et al. 2006

The Journal of Immunology

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Heat shock proteins (Hsp) are markedly up-regulated at sites of inflammation during autoimmune diseases like experimental autoimmune encephalomyelitis (EAE). In this study, we show that Hsp70-peptide complexes (pc) isolated from brains of mice with EAE prevented the development of EAE clinically and pathologically when administered before proteolipid protein 139–151 (PLP139–151) immunization. In contrast, pure Hsp70 or Hsp70-pc derived from brains of healthy mice or other inflamed tissue did not modulate the expression of EAE. In animals in which EAE had been suppressed by Hsp70-pc, lymphocytes showed increased cell death in response to PLP139–151 that correlated with elevated IFN-γ and NO production. Coculture of spleen cells from Hsp70-pc immunized mice with spleen cells from untreated EAE mice, in addition to depletion experiments, showed that NK cells reduced reactivity to PLP139–151. Transfer of NK cells from Hsp70-pc-immunized mice to recipients sensitized for EAE abolished disease development. Thus, we propose that Hsp70 demonstrate the ability to bind to peptides generated during brain inflammation and to induce a regulatory NK cell population that is capable of preventing subsequent autoimmunization for EAE.

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Section: Discussionsupporting

confidence: 89%

Brain-Derived Heat Shock Protein 70-Peptide Complexes Induce NK Cell-Dependent Tolerance to Experimental Autoimmune Encephalomyelitis

Gałązka

Stasiołek

Walczak

et al. 2006

The Journal of Immunology

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“…Secondly, studies in humans and animal models have clearly demonstrated a regulatory role of NK cells in the initiation and progress of autoimmune disorders (11,12). Decreased NK cell activity and numbers are found in patients with multiple sclerosis (MS) (13,14), rheumatoid arthritis (15), and systemic lupus erythematosus (16). In the animal model of MS, depletion of NK cells from C57BL/6 (B6) mice with anti-NK1.1 Ab resulted in a more severe form of T cell-mediated experimental autoimmune encephalomyelitis (EAE) with relapse (17).…”

Section: Nk Cells Inhibit T Cell Proliferation Via P21-mediated Cellmentioning

confidence: 99%

NK Cells Inhibit T Cell Proliferation via p21-Mediated Cell Cycle Arrest

Trivedi

Roberts

Wolf

et al. 2005

The Journal of Immunology

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NK cells have been shown to influence immune responses via direct interaction with cells of the adaptive immune system, such as dendritic cells, B cells, and T cells. A role for NK cells in down-regulation of T cell responses has been implicated in several studies; however, the underlying mechanism of this suppression has remained elusive. In this study we show that dark Agouti rat NK cells inhibit syngeneic T cell proliferation via up-regulation of the cell cycle inhibitor, p21, resulting in a G0/G1 stage cell cycle arrest. The inhibition is cell-cell contact dependent, reversible, and Ag nonspecific. Interestingly, NK cells do not inhibit IL-2 secretion or IL-2R up-regulation and do not induce T cell death. Thus, our results show that NK cells do not affect early T cell activation events, but specifically inhibit T cell proliferation by direct interaction with T cells. Our findings suggest that NK cells may play an important role in maintaining immune homeostasis by directly regulating clonal expansion of activated T cells. This novel mechanism of T cell regulation by NK cells provides insight into NK cell-mediated regulation of adaptive immunity and provides a mechanistic link between NK cell function and suppression of T cell responses.

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“…In humans, several autoimmune disorders such as multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus are associated with decreased NK activity (4,8,14). Other reports have demonstrated that NK cells, particularly those high in CD56, play a role in the regulation of T cells (2,17).…”

mentioning

confidence: 99%

Natural Killer Cells Regulate T-Cell Proliferation during Human Parainfluenza Virus Type 3 Infection

Noone

Paget

Lewis

et al. 2008

J Virol

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Human parainfluenza virus type 3 (HPIV3) is a major respiratory pathogen in humans. Failure to induce immunological memory associated with HPIV3 infection has been attributed to inhibition of lymphocyte proliferation. We demonstrate that the inability of mixed lymphocytes to respond to virally infected antigenpresenting cells is due to an interleukin-2-dependent, nonapoptotic mechanism involving natural killer (NK) cells and their influence is exerted in a contact-dependent manner. These results suggest a novel regulatory mechanism for NK cells during HPIV3 infection, offering an explanation for viral persistence and poor memory responses.

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Clinical relapses of multiple sclerosis are associated with ‘novel’ valleys in natural killer cell functional activity

Cited by 80 publications

References 36 publications

Brain-Derived Heat Shock Protein 70-Peptide Complexes Induce NK Cell-Dependent Tolerance to Experimental Autoimmune Encephalomyelitis

Brain-Derived Heat Shock Protein 70-Peptide Complexes Induce NK Cell-Dependent Tolerance to Experimental Autoimmune Encephalomyelitis

NK Cells Inhibit T Cell Proliferation via p21-Mediated Cell Cycle Arrest

Natural Killer Cells Regulate T-Cell Proliferation during Human Parainfluenza Virus Type 3 Infection

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