B-lymphocyte proliferation during bovine leukemia virus-induced persistent lymphocytosis is enhanced by T-lymphocyte-derived interleukin-2.
Bovine leukemia virus (BLV)-induced persistent lymphocytosis is characterized by a polyclonal expansion of CD5+ B lymphocytes. To examine the role of the cytokine microenvironment in this virus-induced B-lymphocyte expansion, the expression of interleukin-2 (IL-2), IL-4, IL-10, and gamma interferon (IFN-gamma) mRNA, was measured in stimulated peripheral blood mononuclear cells from persistently lymphocytotic BLV-infected cows, nonlymphocytotic BLV-infected cows, and uninfected cows. IL-2 and IL-10 mRNA expression and IL-2 functional activity were significantly increased when peripheral blood mononuclear cells from persistently lymphocytotic cows were stimulated with concanavalin A (ConA). Additionally, during persistent lymphocytosis, peak IL-2 and IL-10 mRNA expression was delayed, and elevated expression was prolonged. To determine the potential biologic importance of increased IL-2 and IL-10 expression, the response of isolated B lymphocytes from persistently lymphocytotic cows to human recombinant cytokines and to cytokine-containing supernatants from isolated T lymphocytes was examined. While recombinant human IL-10 (rhIL-10) did not consistently induce detectable changes, rhIL-2 increased viral protein (p24) and IL-2 receptor expression in isolated B lymphocytes from persistently lymphocytotic cows. Additionally, rhIL-2 and supernatant from ConA-stimulated T lymphocytes enhanced B-lymphocyte proliferation. The stimulatory activity of the T-lymphocyte supernatant could be completely inhibited with a polyclonal anti-rhIL-2 antibody. Finally, polyclonal anti-rhIL-2 antibody, as well as anti-BLV antibody, inhibited spontaneous proliferation of peripheral blood mononuclear cells from persistently lymphocytotic cows, demonstrating that the spontaneous lymphoproliferation characteristic of BLV-induced persistent lymphocytosis is IL-2 dependent and antigen dependent. Collectively, these findings strongly suggest that increased T-lymphocyte expression of IL-2 in BLV-infected cows contributes to development and/or maintenance of persistent B lymphocytosis.
Trueblood
E S
ES
Department of Veterinary Microbiology and Pathology, Washington State University, Pullman 99164, USA. est@vetmed.wsu.edu
Brown
W C
WC
Palmer
G H
GH
Davis
W C
WC
Stone
D M
DM
McElwain
T F
TF
D000818:Animals; D000956:Antigens, Viral / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology*; D002417:Cattle; D002455:Cell Division; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D017077:Culture Media, Conditioned; D015870:Gene Expression; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D007700:Kinetics; D001909:Leukemia Virus, Bovine / Q000502:physiology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008218:Lymphocytosis; D008934:Mitogens / Q000494:pharmacology; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000378:metabolism*; D014758:Viral Core Proteins / Q000096:biosynthesis
D000956:Antigens, Viral; D017077:Culture Media, Conditioned; D007376:Interleukin-2; D008934:Mitogens; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D014758:Viral Core Proteins; C089189:core protein p24, bovine leukemia virus; D003208:Concanavalin A; D016753:Interleukin-10