Relationship of persistent lymphocytosis, antibody titers, and proviral load with expression of interleukin-12, interferon-γ, interleukin-2, interleukin-4, interleukin-10, and transforming growth factor-β in cows infected with bovine leukemia virus from a high-prevalence dairy complex.

Abstract

Bovine leukemia virus (BLV) subclinical infection promotes persistent lymphocytosis (PL), which is related to susceptibility and progression to lymphoma. Moreover, lymphocyte counts directly correlate with BLV antibody titers and proviral load, and cell immune responses are considered atypical due to immune suppression. In order to determine the relationship of PL, antibody titers, and proviral load with interleukin (IL)-12, interferon (IFN)-γ, IL-2, IL-4, IL-10, and transforming growth factor (TGF)-β expression in a 3-month interval, 58 cows were selected (30 BLV⁺ and 28 BLV^-) from a high-prevalence dairy herd to complete 3 monthly blood samplings for the assessment of PL, BLV antibody titers, BLV proviral load, and IL-12, IFN-γ, IL-2, IL-4, IL-10, and TGF-β expression. At sampling conclusion, the BLV-infected cows were grouped according to PL, BLV proviral load, and BLV antibody titers as follows: BLV⁺PL⁺ (n = 16) and BLV⁺PL^- (n = 14); high proviral load (HPL) (n = 18) and low proviral load (LPL) (n = 13); high antibody titers (HAT) (n = 17) and low antibody titers (LAT) (n = 14). The BLV⁺PL⁺ cows showed significantly higher proviral load and antibody titers than the BLV⁺PL^- group; however, the former suggested spread presumably unrelated to lymphoma outcome, because HPL was observed in PL^- cows in the last sampling. Consistent with the data, a higher antibody response strongly indicated BLV susceptibility since it was linked to PL⁺ occurrence and a cytokine profile compatible with immune suppression. Furthermore, a reversion to lower antibody titers was observed in cows with HPL far ahead of time, most likely due to long-term immune suppression. In addition, high expression of IL-10 and TGF-β was associated with reduced IL-12, IFN-γ, IL-2, and IL-4 expression alongside PL, HAT, and HPL in BLV-infected cows, suggesting an IL-10- and TGF-β-induced immune suppression. The IL-10 expression was increasing throughout, implying disease progression, as described. In conclusion, the proliferative expansion of lymphocytes known as PL might enhance a regulatory-rich cell population (Bregs and/or Tregs) that secretes IL-10 and TGF-β, leading to immune suppression. Further studies must be conducted regarding the types of regulatory cells involved in BLV-induced immune suppression.