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Efficient induction of immediate tolerance to contact sensitivity by hapten-modified spleen cells requires Ia+ cells compatible with recipient

Nature volume 278, pages 257–259 (1979)Cite this article

Abstract

IMMUNOLOGICAL distinction between ‘self’ and ‘non-self’ is important in maintaining normal homeostasis: a breakdown in this regulation probably results in auto-destructive processes. Recent developments in cellular immunology have shown that the induction of an immune response (sensitisation) involves the recognition of antigen in combination with products of the major histocompatibility complex (MHC)1,2. In this context, it is pertinent to ask whether the induction and maintenance of specific immunological unresponsiveness (tolerance) to foreign antigens is also under genetic control. Contact sensitivity and tolerance to simple chemical compounds (haptens) in mice has provided insight into the complex cellular interactions involved in the unresponsive state3–5. Parenteral injection of the reactive haptens 1-fluoro-2,4-dinitrobenzene (DNFB) or its sulphonate (DNBS) before epicutaneous sensitisation with DNFB results in unresponsiveness3,4. This process seems to be mediated by at least two mechanisms, clonal inhibition and induction of suppressor T cells (Ts)6, both of which can be induced by either DNBS or DNFB coupled in vitro to red blood cells (DNP-RBC). The maximum tolerant state then develops 4–7 d after injection. However, another tolerogen, DNFB coupled in vitro to spleen cells (DNP-SC), produces maximum unresponsiveness immediately. This rapid induction of unresponsiveness was shown to be independent of Ts and thus was referred to as clonal inhibition6. The dichotomy between syngeneic DNP-SC and DNP-RBC in their ability to tolerise immediately was first thought to be due to either different homing characteristics or cell surface components4. With respect to the latter, an intriguing difference between the two tolerogens is the lack of I-region associated (Ia) antigens (of the MHC) on the surface of red blood cells7,8. We have investigated this difference by tolerising mice with DNP-SC depleted of Ia+ cells or with DNP-SC from donors which are I-region incompatible with respect to the recipient animal. The results reported here indicate that the induction of immediate tolerance requires I-region compatibility between the donor of the DNP-SC tolerogen and the recipient.

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Authors and Affiliations

  1. Departments of Microbiology and Immunology and Medicine, University of Colorado Medical Center, Box B-175, 4200 East Ninth Avenue, Denver, Colorado, 80262

    PAUL J. CONLON, JOHN W. MOORHEAD & HENRY N. CLAMAN

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  1. PAUL J. CONLON
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  2. JOHN W. MOORHEAD
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  3. HENRY N. CLAMAN
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CONLON, P., MOORHEAD, J. & CLAMAN, H. Efficient induction of immediate tolerance to contact sensitivity by hapten-modified spleen cells requires Ia+ cells compatible with recipient. Nature 278, 257–259 (1979). https://doi.org/10.1038/278257a0

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