[The interrelation of the expression of HLA class I and II proteins and of the costimulatory proteins CD11a/CD18 and CD16 with the lytic activity of resting and activated natural killer lymphocytes].
It has been presumed that: 1) rheumatoid arthritis (RA) is a genuine model of activation of the peripheral natural killers (NK); 2) methods of NK separation can cause their activation, and therefore only peripheral mononuclear cells were used. The aim of this research was to study the role of cytolysis of HLA-I, HLA-DR, and costimulatory proteins CD11a and CD16 expressed on resting and activated peripheral NK cells. A total of 74 healthy volunteers (HV) and 74 RA patients were compared before corticosteroid or gold treatment. Two-colour immunofluorescence and cytofluorimetric analysis, cytotoxic test against the target K 562 cells (class I negative) before and after incubation of PMC with monoclonal antibodies (MoAB) to HLA-I (E3D8), HLA-DR (ICO-1), CD11 (ICO-11), PXx63 Ag8.653 as control, and also incubation with recombinant alpha 2-IFN were used. VEP-13 MoAB was used for CD16 determination. Compared with HV PMC, the RA PMC showed a statistically significant increase of activated NK lymphocytes (CD11a+DR+ and CD16+DR+ by 2.03 and 1.96 times, resp.), and increased level of expression of HLA-I, HLA-DR, and CD16 on CD11a+ lymphocytes, resulting in significantly diminished cytolytic activity (CA) by 1.9 times. A short-term incubation with alpha 2-IFN (100 U/ml, 1 h) increased the level of expression of HLA- and costimulatory proteins and the CA of the HV PMC, while the RA PMC did not react. HV peripheral NK are concluded to be mainly resting cells, and the RA peripheral NK are mainly the activated ones. Only using the level of expression of HLA-DR on CD11a lymphocytes, as a ranking criterion, allowed to reveal two types of correlation between the CA and immunocytological parameters of PMC. The first type: in HV, the CA correlated positively (P < 0.025) with the percentage of CD11a+CD16+, and with levels of expression of HLA-I (P < 0.025) and CD16 (P < 0.025) expressed on CD11a lymphocytes (5-9.5 MFI DR--the mean fluorescence intensity of HLA-DR). The second type: the CA positively correlated (P < 0.05) with the percentage of CD11a+CD16-, and with levels of expression of HLA-DR (P < 0.05) and CD11a (P < 0.05) expressed on CD11a lymphocytes (12.4-16 MFI DR). In RA patients with a "normal" density expression of HLA-DR on CD11a lymphocytes (up to 14 MFI) there exists a mixed type: the CA correlated positively (P < 0.05) with the percentage of CD11a+CD16+, and with levels of expression of HLA-DR (P < 0.05) and CD11a (P < 0.05) expressed on CD11a lymphocytes. In RA patients with a very high density expression of HLA-DR on CD11a lymphocytes (VH-DR group, 18-26 MFI) the CA correlated negatively with the percentage of CD11a+CD1 6+ (P < 0.05), and with levels of expression of HLA-DR (P < 0.025) and CD11a (P < 0.025) expressed on CD11a lymphocytes. The anti-HLA-I,-DR, -CD11a MoABs strongly inhibit the Ca in HV- and RA-PMC. However, in the VH-DR group the anti-DR MoAB stimulates the CA from 27.06 +/- 10.25 up to 41.69 +/- 14.23%. Thus, activated peripheral CD11a+CD16+ lymphocytes suppress the CA of other NK.
Musatov
M I
MI
Institute of Clinical Immunology, Siberian Branch of the Academy of Medical Sciences, Novosibirsk.
Petrova
E D
ED
Konenkov
V I
VI
D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000276:immunology; D018821:CD18 Antigens / Q000187:drug effects / Q000276:immunology*; D002460:Cell Line; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology*; D005260:Female; D006684:HLA-DR Antigens / Q000187:drug effects / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000187:drug effects / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000187:drug effects / Q000276:immunology*; D008297:Male; D017452:Receptors, IgG / Q000187:drug effects / Q000276:immunology*; D011994:Recombinant Proteins; D013997:Time Factors
D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D006684:HLA-DR Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007370:Interferon Type I; D016169:Lymphocyte Function-Associated Antigen-1; D017452:Receptors, IgG; D011994:Recombinant Proteins
Vzaimosviaz' ékspressii HLA-belkov I i II klassov i kostimuliatornykh belkov CD11a/CD18 i CD16 s liticheskoĭ aktivnost'iu pokoiashchikhsia i aktivirovannykh estestvennykh killernykh limfotsitov.