IMMUNOGENETIC MECHANISMS OF RESISTANCE TO PERSISTENT LYMPHOCYTOSIS IN BOVINE LEUKEMIA VIRUS-INFECTED CATTLE

Department of Animal Sciences 206 Edward R. Madigan Laboratory 1201 W. Gregory Drive Urbana, IL 61801

The association between bovine major histocompatibility complex class II DRB3 (BoLA-DRB3) alleles and resistance to the subclinical progression of bovine leukemia virus (BLV) infection has been documented in different herds and breeds throughout the world. Although dominant resistance to the spread of BLV in vivo is known to be related to the presence of glutamic acid and arginine at positions 70-71 of the DRB3 molecule, the immunological mechanism(s) by which DRB3 and/or closely linked genes exert their effect(s) is not known. To clarify the mechanism of host resistance to BLV we experimentally infected 5 Holstein-Friesian cows with resistance-associated genotypes and 5 age- and breed matched cows with susceptibility- associated genotypes. During a one year period post-infection, several measures of subclinical infection and immunological function were measured, including anti-gag antibody titer, proviral load, differential count, peripheral B-cell concentration, T-cell proliferative responses to BLV antigens and peptides, and mRNA for IFN-gamma , IL-2, IL-4 and IL-10 produced by T cells in response to these antigens. Cows with resistance and susceptibility-associated genotypes followed a similar subclinical course of infection up to approximately 10 weeks post-infection, after which proviral load, antibody titer to gag antigen and lymphocyte count dramatically declined in cows having resistance-associated alleles. Cows with resistance-associated alleles showed significantly greater IL-2 and IL-4 responses to BLV antigens and specific peptides at 2 weeks post-infection and then again after 10 weeks. These results demonstrate that genetically resistant animals are generally high-responders to BLV antigens, but more importantly, that cellular immunity to BLV plays a major role in BoLA-mediated resistance to the subclinical progression of BLV infection.