Natural killer receptors distribution in multiple sclerosis: Relation to clinical course and interferon-beta therapy

Clin Immunol. 2010 Oct;137(1):41-50. doi: 10.1016/j.clim.2010.06.002. Epub 2010 Jun 26.

Abstract

NK cell receptors (NKR) are expressed in subsets of NK and CD8+ T cells, lymphocytes involved in multiple sclerosis (MS) pathogenesis. Clinical implications of NKR expression in MS are unknown. Here, we show that the proportions of CD8+ T cells displaying LILRB1, an inhibitory NKR expressed at late stages of T cell differentiation, were directly related with age and MS duration, and inversely with the immunomodulatory therapy-dependent increase of CD56(bright) NK cells. Similar associations were found for KIR+ and CD56+ CD8+ T cells, whereas no age-related NKR distribution was perceived in controls. Moreover, active MS had lower LILRB1+ NK cells, and IFN-β-treated patients exhibited a phenotypic profile related to shorter disease evolution. Progressive accumulation of terminally differentiated T lymphocytes and experienced NK cells in MS, presumably stimulated in response to a persistent challenge and modulated by IFN-β therapy, may support the analysis of NKR distribution as new biomarkers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aging / metabolism
  • Antibodies / blood
  • Antibodies / immunology
  • Antigens, CD / metabolism*
  • Biomarkers / metabolism
  • CD56 Antigen / metabolism
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Count
  • Cytomegalovirus Infections / diagnosis
  • Cytomegalovirus Infections / immunology
  • Female
  • Humans
  • Interferon-beta / therapeutic use*
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / metabolism
  • Leukocyte Immunoglobulin-like Receptor B1
  • Leukocytes, Mononuclear / cytology
  • Lymphocytes / cytology
  • Lymphocytes / drug effects
  • Lymphocytes / metabolism*
  • Male
  • Middle Aged
  • Multiple Sclerosis / diagnosis
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / immunology*
  • Multiple Sclerosis / metabolism
  • Multiple Sclerosis, Chronic Progressive / diagnosis
  • Multiple Sclerosis, Chronic Progressive / drug therapy
  • Multiple Sclerosis, Chronic Progressive / immunology
  • Multiple Sclerosis, Chronic Progressive / metabolism
  • Multiple Sclerosis, Relapsing-Remitting / diagnosis
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy
  • Multiple Sclerosis, Relapsing-Remitting / immunology
  • Multiple Sclerosis, Relapsing-Remitting / metabolism
  • NK Cell Lectin-Like Receptor Subfamily C / metabolism
  • Receptors, Immunologic / metabolism*
  • Receptors, KIR / metabolism
  • Receptors, Natural Killer Cell / metabolism*
  • Recurrence
  • Time Factors

Substances

  • Antibodies
  • Antigens, CD
  • Biomarkers
  • CD56 Antigen
  • KLRC1 protein, human
  • LILRB1 protein, human
  • Leukocyte Immunoglobulin-like Receptor B1
  • NK Cell Lectin-Like Receptor Subfamily C
  • Receptors, Immunologic
  • Receptors, KIR
  • Receptors, Natural Killer Cell
  • Interferon-beta