Cell-to-cell contact not soluble factors mediate suppression of lymphocyte proliferation by bovine parainfluenza virus type 3.
We have previously characterized the ability of parainfluenza virus type 3-infected (PIV-3) and noninfected bovine alveolar macrophages (BAM) to support lymphocyte proliferation. While uninfected macrophages support proliferation of lymphocytes stimulated with concanavalin A (Con A), ovalbumin, and interleukin 2 (IL-2), lymphocyte [3H]thymidine incorporation was suppressed in the presence of PIV-3-infected BAM. Since viral infection of macrophages has been shown to alter arachidonic acid metabolism and cytokine secretion, we have determined if arachidonate metabolism or the lack of IL-1 and IL-2 mediated the suppression of lymphocyte proliferation by PIV-3. Inhibition of arachidonic acid metabolism failed to reverse the suppressive effect of viral infection as did supplementation of cultures with bovine recombinant IL-1 beta, IL-2, or lymphocyte-conditioned medium. Further, lymphocytes proliferated normally when physically separated from virus infected BAM by a semipermeable membrane. Stimulation of lymphocytes in contact with infected BAM resulted in marked suppression of lymphocyte [3H]thymidine incorporation. Interactions between stimulated lymphocytes and PIV-3-infected BAM resulted in PIV-3 infection of lymphocytes. Virus infection of lymphocytes was confirmed ultrastructurally by the presence of characteristic parainfluenza virus inclusions and virus budding from lymphocyte plasma membranes. It was concluded that suppression of lymphocyte proliferation by PIV-3 is mediated in part by infection of stimulated lymphocytes during cell-to-cell contact with BAM.
Basaraba
R J
RJ
Department of Veterinary Diagnostic Investigation, College of Veterinary Medicine, Kansas State University, Manhattan 66506-5660, USA.
Laegreid
W W
WW
Brown
P R
PR
Silflow
R M
RM
Brown
R A
RA
Leid
R W
RW
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002417:Cattle; D002450:Cell Communication; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003588:Cytopathogenic Effect, Viral; D007108:Immune Tolerance; D007181:Inclusion Bodies, Viral; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology; D007376:Interleukin-2 / Q000378:metabolism / Q000494:pharmacology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000821:virology; D008264:Macrophages / Q000187:drug effects / Q000821:virology*; D008297:Male; D010224:Parainfluenza Virus 3, Human / Q000276:immunology* / Q000302:isolation & purification
D017077:Culture Media, Conditioned; D007375:Interleukin-1; D007376:Interleukin-2; D003208:Concanavalin A; D016718:Arachidonic Acid