γδ T cell knockout chickens as a model to investigate the T cell response against Infectious Bursal Disease infection

T cells are involved in viral clearance and the recovery of the primary B cell organ, the bursa of Fabricius (BF), after infection of young chickens with infectious bursal disease virus (IBDV). It is not clear which T cell subtypes specifically contribute to this process. To investigate the possible role of γδ T lymphocytes in virus control, we compared the IBDV pathogenesis between 3-week-old γδ T cell receptor (TCR Cγ^-/-) knockout (KO) and wild-type chickens (WT) after inoculation with an intermediate plus IBDV strain. At 3 (experiment (E) 1, E3), 7 (E1), 21 (E2, E3) and 28-days (E3) post-inoculation (dpi), birds from IBDV-inoculated and virus-free groups were necropsied. Samples of the BF were evaluated for histological lesion development and recovery, as well as IBDV-antigen and T cell subtype distribution. Three intrabursal T cell profiles were analyzed with the principal component analysis to summarize data dimensions including cytotoxic T cells, T-helper1 cells (Th1) and regulatory T cells (T_reg). At 3 and 7 dpi, the average bursal lesion development and intrabursal antigen load were comparable between both inoculated groups. At 3 dpi, more intrabursal Th1, T_regs and cytotoxic T cells were observed in IBDV-inoculated KO chickens compared to inoculated WT birds. Interestingly, at 21 dpi, IBDV-infected KO chickens showed a faster viral clearance and earlier bursal recovery. This coincided with less intrabursal Th1 and T_regs in KO chickens compared to WT chickens. Our data suggests that the lack of γδ T lymphocytes may be compensated in IBDV-inoculated KO chickens by an increased number of intrabursal αβ T lymphocytes compared to virus-inoculated WT birds, allowing better control of IBDV infection and providing circumstantial evidence that αβ T lymphocytes may impact IBDV pathogenesis more than γδ T lymphocytes.