Reduced IL-2 and IL-4 mRNA expression in CD4+ T cells from bovine leukemia virus-infected cows with persistent lymphocytosis.
The role of T-helper (Th) responses in the subclinical progression of bovine leukemia virus (BLV) infection was explored by determining the contribution of CD4+ T cells to the expression of mRNAs encoding interferon-gamma (IFN-gamma), interleukin-2 (IL-2), interleukin-4 (IL-4), and interleukin-10 (IL-10) in BLV-infected cattle. Relative levels of mRNA encoding IFN-gamma, IL-2, IL-4, and IL-10 were measured in fresh and concanavalin A (Con A) activated peripheral blood mononuclear cells (PBMCs) and purified CD4+ T cells from cows seronegative to BLV (BLV-), seropositive without persistent lymphocytosis (BLV+PL-), and seropositive with PL (BLV+PL+) using a semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) assay. The expressions of IFN-gamma, IL-2, and IL-4 mRNAs were significantly reduced in the PBMCs from BLV+PL+ cows as compared to BLV- cows. Reduced levels of IL-2 and IL-4 mRNAs were detected in fresh CD4+ T cells from BLV+PL+ cows. In contrast, Con A stimulated PBMCs and CD4+ T cells did not differ significantly in expression of IFN-gamma, IL-2, IL-10, or IL-4 mRNAs among the BLV infection groups. Using flow-sorted CD4+ T cells and semiquantitative RT-PCR the frequencies of CD4+ T cells transcribing IFN-gamma, IL-2, IL-4, and IL-10 mRNAs in the peripheral blood of BLV-, BLV+PL-, and BLV+PL+ cows were determined. There were no significant differences in the frequencies of CD4+ T cells expressing these cytokine mRNAs among animals in the different BLV infection categories. Thus, the observed differences in IL-2 and IL-4 mRNAs in CD4+ T cells were due to changes in steady-state mRNA levels expressed by individual cells and not to changes in the frequency of cells transcribing IL-2 and IL-4 mRNAs. These results demonstrate that the progression of BLV infection to PL is associated with reduced expression of classical Th1 and Th2 cytokines by CD4+ T cells, thus suggesting aberrant Th regulation in subclinically infected animals.
Amills
Marcel
M
Departments of Animal Sciences, Laboratory of Immunogenetics, University of Illinois at Urbana-Champaign, Illinois 61801, USA.
Ramiya
Vijayakumar
V
Norimine
Junzo
J
Olmstead
Colleen A
CA
Lewin
Harris A
HA
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002417:Cattle; D016583:Enzootic Bovine Leukosis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D005260:Female; D015870:Gene Expression; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D001909:Leukemia Virus, Bovine; D008218:Lymphocytosis / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis
D007376:Interleukin-2; D012333:RNA, Messenger; D015847:Interleukin-4