LACK OF ORAL TOLERANCE IN C3H/HeJ MICE

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LACK OF ORAL TOLERANCE IN C3H/HeJ MICE (1)

Oral toleranceto solubleantigenhasalsobeenattributedto theinductionof T8cellsin thegut-associatedlymphoreticulartissue(GALT), e.g.,Peyer’spatches. High IgA immune responses to orally administered,thymic-dependent(TD) antigen occur in lipopolysaccharide(LPS)-non responsive C3H/HeJ mice, and this response is due to enhanced production of T helper (Th) cells in GALT.

The three LPS-responsive mouse strains tested did not respond to SRBC, whereas C3H/HeJ mice elicited IgM, IgG, and IgA anti-SRBC PFC response. Oral administration of SRBC for 2 wk to LPS-responsive mice results in oral tolerance, whereas similar treatment of C3H/HeJ mice primes these animals for anamnestic response.

Low anti-TNP PFC responses were seen in B cell cultures containing T cells from C3H/HeN spleen or PP. Treatment of C3H/HeJ splenic or PP T cells with anti-Lyt-l.1 and C completely abrogated in vitro B cell responses, whereas similar treatment of T cells with anti-Lyt-2.1 and C gave heightened anti-TNP PFC response. These responses were lower than those seen in cultures containing identically treated C3H/HeJ T cells. Significant numbers of Th cells are present in the PP and spleen of orally treated C3H/HeJmice, but less Th cell activity is seen in identically treated C3H/HeN mice.

T~ cells probably originate in PP and mediate lack of systemic responses in lymphoid tissues such as spleen was provided by experiments demonstrating that prior treatment of dissociated PP or spleen cells from C3H/HeN mice given SRBC by GI for 14 d with anti-Lyt-2.1 and C abrogated unresponsiveness. Higher IgA responses occurred in PP cultures treated with anti-Lyt-2.1. Similar results were obtained when either PP or spleen cells from BALB/c mice given SRBC by GI for prolonged periods were treated with an anti-Lyt-2 antibody to remove the Lyt-2,3 + T cell population.

Daily gastric intubation of lipopolysaccharide (LPS)-responsive C3H/HeN, BALB/c, and Swiss mice with SRBC for 2 wk resulted in oral tolerance, whereas similarly treated LPS-nonresponsive C3H/HeJ mice gave splenic anti-SRBC PFC responses, including the IgA isotype, after systemic challenge with antigen.

1. H. Kiyono, J. R. McGhee, M. J. Wannemuehler, S. M. Michalek, Lack of oral tolerance in C3H/HeJ mice. J. Exp. Med. 155, 605–610 (1982).

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