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- Schepis, Danika, et al.
(författare)
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Increased proportion of CD56bright natural killer cells in active and inactive systemic lupus erythematosus
- 2009
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Ingår i: Immunology. - : Wiley. - 0019-2805 .- 1365-2567. ; 126:1, s. 140-6
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Tidskriftsartikel (refereegranskat)abstract
- Natural killer (NK) cells belong to the innate immune system but can also affect adaptive immune reactions. This immune regulatory function is often ascribed to the CD56(bright) subpopulation of NK cells that is prevalent in secondary lymphoid tissues and has potent cytokine-producing ability. The NK cells have been described as affecting autoimmune disease and stimulating B-cell production of antibodies, but their role in systemic lupus erythematosus (SLE) pathology has not been extensively studied. We have studied NK cells in SLE, a B-cell-driven systemic autoimmune disease, and phenotypically characterized peripheral blood NK cells in comparison to NK cells from patients with immunoglobulin A nephritis, rheumatoid arthritis and healthy individuals. We have found an increased proportion of CD56(bright) NK cells in SLE, regardless of disease activity. We detected a somewhat increased expression of the activating receptor NKp46/CD335 on NK cells from SLE patients, although neither the percentage of NK cells of all lymphocytes nor the expression of other NK receptors analysed (LIR-1/CD85j, CD94, NKG2C/CD159c, NKG2D/CD314, NKp30/CD337, NKp44/CD336, CD69) differed between patient groups. We show that type I interferon, a proinflammatory cytokine known to be abundant in SLE, can cause increases of CD56(bright) NK cells in vitro. We confirmed that serum levels of interferon-alpha were increased in active, but not in inactive, disease in the SLE patient group. In conclusion, we found an increased proportion of CD56(bright) NK cells in the blood of SLE patients, although it remains to be examined whether and how this relates to the disease process.
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| 2. |
- Schepis, Danika
(författare)
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Innate and adaptive immune responses in viral and chronic inflammatory diseases
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this thesis I address some important questions regarding innate and adaptiveimmune responses in different human diseases. We analysed two distinctconditions: chronic autoimmune inflammation, specifically SLE, and chronic viralinfection, represented by herpes simplex virus (HSV). The role of differentcomponents of the immune system were addressed, ranging from innate factors,such as IFN-alpha and NK cells, to the adaptive immune system, represented by Tcells.The results are discussed with respect to the various possible levels ofinteraction between the innate and the adaptive immune systems. We first focused on a specific subset of NK cells, CD56bright NK cells, which isnormally found in lymphoid tissue and at sites of inflammation and which, uponactivation, has the capacity to produce large amounts of cytokines. CD56bright NKcells are often discussed in relation to their possible role in shaping adaptiveimmune responses. The proportion of CD56bright NK cells was significantlyincreased in blood in subjects affected by SLE. This finding was not dependent ondisease activity and may be due to increased levels of IFN-alpha, a typical hallmarkof SLE patients. We then investigated several aspects of herpes virus infections. We describe apossible role for the activating NK cell receptor NKG2D in the immune responseagainst HSV1 infection. We determined that HSV1 has the ability to downregulatethe cell surface expression of NKG2D ligands of infected cells. We also observedthat NK cells from patients affected by recurrent HSV1 manifestations haveslightly increased levels of expression of NKG2D on blood NK cells during theacute phase of viral reactivation. In a prospective clinical study of patients withHSV genital infection, we observed that low specific T-cell responses against HSV-antigens during primary HSV1 and 2 infection predict a high frequency of clinicalrecurrences. Finally we examined the immune response of patients affected byrecurrent meningitis caused by HSV2 infection. During asymptomatic periods,these patients showed elevated expression of TLR3 and TLR9, elevated IFN-alphaproduction to certain stimuli and elevated specific T-cell responses when comparedto patients with recurrent genital infection and to healthy seropositive donors. Inaddition, there were qualitative differences in their T-cell cytokine profile. Weconclude that HSV2 meningitis is likely not a consequence of an impaired antiviralinnate or adaptive immune sponse at the systemic level.
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