Oral and portal venous tolerance in the IFN-gamma knockout (GKO) mouse

Abstract

We investigated the effect of both oral and portal venous administration of alloantigen on the systemic delayed type hyper-sensitivity (DTH) response to alloantigen rechallenge in GKO mice. C57BL/6 (B6) control and GKO mice were given either saline or BALB/c spleen cells (SC) by oral gavage (PO) or by injection into the portal vein (PV) on day 0. Injection of BALB/c SC SQ was performed after 7 days followed by footpad injection of BALB/c SC on day 14. Footpad swelling was measured 24 hours later using a micrometer. While B6 mice given PO or PV saline demonstrated a DTH response of 0.47 ± 0.04 mm and 0.49 ± 0.05 mm, respectively, in GKO mice, a greater DTH response of 0.72 ± 0.08 mm and 0.75 ± 0.05 mm was measured after either PO or PV saline (p < 0.05, p < 0.05, respectively). Despite this heightened response in control GKO mice, the DTH response was completely suppressed in both GKO and B6 mice, following both PO and PV BALB/c feedings (p < 0.001, p < 0.001, respectively in both GKO and B6). The unchanged brisk response to third party C3H/HeJ demonstrated antigenic specificity. While DTH responsiveness to alloantigen is increased in the absence of IFN-γ both oral and portal venous alloantigen-specific tolerance can still be established similar to that in control B6 mice. Achievement of a tolerogenic immune response by both oral and portal venous routes indicates that IFN-γ does not influence tolerance induction. TABLE—ABSTRACT P26MouseAntigen (route)SQ antigenFootpad swelling (mm)B6Saline (PO)BALB/c0.47 ± 0.04B6BALB/c (PO)BALB/c0.02 ± 0.01B6BALB/c (PO)C3H/HeJ0.52 ± 0.09B6Saline (PV)BALB/c0.49 ± 0.05B6BALB/c (PV)BALB/c0.01 ± 0.01B6BALB/c (PV)C3H/HeJ0.44 ± 0.06GKOSaline (PO)BALB/c0.72 ± 0.08GKOBALB/c (PO)BALB/c0.02 ± 0.00GKOBALB/c (PO)C3H/HeJ0.77 ± 0.11GKOSaline (PV)BALB/c0.75 ± 0.05GKOBALB/c (PV)BALB/c0.03 ± 0.02GKOBALB/c (PV)C3H/HeJ0.70 ± 0.05