Differential interleukin-2 and interferon-gamma production by human lymphocyte cultures exceptionally resistant to Epstein-Barr virus immortalization.
Epstein-Barr virus (EBV) readily immortalizes human peripheral blood lymphocytes (PBL) in vitro. However, during the past several years, we found that PBL from two exceptional EBV-seropositive healthy adult individuals were refractory to immortalization by EBV. We report here a study aimed at learning about the immunobiological features which differentiate these EBV-resistant (R) PBL from others which are susceptible (S) to EBV immortalization. Results of this investigation indicate that: (a) Following EBV infection, R-PBL produced significantly higher amounts of interferon gamma (IFN-gamma) than S-PBL. There were however no differences in regard to interferon alpha production between these two types (R and S) of EBV-infected cultures. (b) R-PBL had a maximal interleukin-2 (IL-2) production by S-PBL occurred at least 48 hr later, i.e., at Day 7. (c) The percentage of non-B cells expressing the IL-2 receptor was also higher in EBV-infected R-PBL than S-PBL. (d) In contrast, expression of IL-2 receptors after EBV infection was higher on B cells from S-PBL than on B cells from R-PBL. Interestingly, no differences were noted in regard to IL-2 receptor expression between R-PBL and S-PBL treated with mitogens (i.e., phytohemagglutinin and pokeweed mitogen). (e) Finally, using anti-IL-2 and anti-IFN-gamma antibodies in EBV-infected R-PBL cultures, we were able to obtain EBV-induced immortalization of these cultures. Taken together, these results suggest that an early IL-2 synthesis and high IFN-gamma production by EBV-infected PBL play an important role against lymphocyte immortalization by EBV.
Gosselin
J
J
Immunology Research Center, Institut Armand-Frappier, Ville de Laval, Québec, Canada.
Menezes
J
J
Mercier
G
G
Lamoureux
G
G
Oth
D
D
D000937:Antigen-Antibody Reactions; D000956:Antigens, Viral / Q000032:analysis; D002455:Cell Division; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D007370:Interferon Type I / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000096:biosynthesis*; D008214:Lymphocytes / Q000382:microbiology / Q000502:physiology*; D015375:Receptors, Interleukin-2 / Q000378:metabolism
D000956:Antigens, Viral; D007370:Interferon Type I; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D007371:Interferon-gamma