Reduced IL-2 and IL-4 mRNA Expression in CD4 + T Cells from Bovine Leukemia Virus-Infected Cows with Persistent Lymphocytosis

Abstract

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-γ (IFN-γ), interleukin-2 (IL-2), interleukin-4 (IL-4), and interleukin-10 (IL-10) in BLV-infected cattle. Relative levels of mRNA encoding IFN-γ, 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-γ, 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-γ, 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-γ, 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.