Cytotoxic mechanisms in vitro against Epstein-Barr virus infected lymphoblastoid cell lines in rheumatoid arthritis.
Impaired regulation of latent infection with Epstein-Barr virus (EBV) may contribute to the pathogenesis of rheumatoid arthritis (RA) by allowing uncontrolled polyclonal B cell activation. The control of EBV infection in vitro is dependent on several cytotoxic lymphoid cell populations. The present report examines the suppression of early lymphoblastoid outgrowth by natural killer (NK) like cells and the ability to form cytotoxic T lymphocytes (CTLs) specific for EBV in vitro. The latter was measured by a regression assay of EBV induced lymphoblastoid transformation. In this assay the regression of B cell outgrowth at four and six weeks is due to the generation of CTLs specific for EBV. Patients with RA were defective in this ability to generate CTLs. Eight out of nine patients with RA had a geometric mean at the 50% regression end point equal to or greater than 20 X 10(5) cells/ml. In contrast, the geometric mean for all control donors was less than 4 X 10(5) cell/ml. NK activity was measured by a conventional 51Cr release assay with K562 targets. Patients with RA did not have significantly different activity from that of controls (RA patients, n = 4, 45.6 +/- 19.7% (means +/- SD) at 50:1, effector:target; normals, n = 5, 56.6 +/- 5.7%). No spontaneous NK activity was detected against allogeneic or autologous EBV infected B cell targets. When peripheral mononuclear cells from patients were incubated for six days with interleukin-2, lysis of EBV infected targets was seen. No difference in this activity was seen between RA and control studies. Overall, these studies show that patients with RA are defective in their ability to generate CTLs specific for EBV in vitro.
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D002460:Cell Line; D002472:Cell Transformation, Viral; D003602:Cytotoxicity, Immunologic; D005260:Female; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D007962:Leukocytes / Q000276:immunology; D008222:Lymphokines / Q000276:immunology; D008297:Male; D008875:Middle Aged; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D008222:Lymphokines