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Resistance to tolerance induction in the diabetes-prone Biobreeding rat as one manifestation of abnormal responses to superantigens

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Summary

T cells taken from normal rats treated with an exogenous source of bacterial superantigen in vivo specifically failed to proliferate following re-stimulation with the same superantigen in vitro. Responsiveness was restored following the addition of an exogenous source of interleukin-2 indicating that the T cells had been made functionally tolerant and not deleted. While staphylococcal enterotoxin treatment of normal rats virtually abolished T-cell proliferation to the same enterotoxin in vitro, T cells from similarly treated diabetes-prone Biobreeding (BB-DP) rats were markedly resistant to this in vivo effect. Responses in BB-DP rats were never reduced by more than 50% even when a 4 times more effective dose of enterotoxin was employed. The resistance of BB-DP peripheral T cells to staphylococcal enterotoxin-induced tolerance could not be attributed to differences in T-cell receptor V beta chain family usage of BB-DP vs normal T cells but was associated with qualitative differences in the way in which BB-DP T cells responded to staphylococcal enterotoxins in vitro. While under optimal stimulatory conditions BB-DP T-cell proliferative responses to staphylococcal enterotoxins appeared comparable to those from non-diabetes-prone animals, under superoptimal conditions BB-DP, but not diabetes-resistant, donor T-cell proliferative responses to staphylococcal enterotoxins could be blocked in vitro with antibodies to CD4 antigens. In addition, BB-DP T-cell proliferative responses were more sensitive to suboptimal staphylococcal enterotoxin doses in vitro. We discuss ways in which abnormal BB-DP T-cell responses to superantigens in general and resistance to staphylococcal enterotoxin-mediated tolerance induction in particular may play a role in the generation of a peripheral T-cell repertoire prone to autoimmunity.

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Abbreviations

SE:

Staphylococcal enterotoxin

BB-DP:

diabetes-prone Biobreeding rat

WF:

Wistar Furth

TCR:

T-cell receptor

VΒ :

variable region beta chain

CΒ :

constant region beta chain

MMTV:

mouse mammary tumour virus

SEB:

staphylococcal enterotoxin B

SEA:

staphylococcal enterotoxin A

SEE:

staphylococcal enterotoxin E

SEC1:

staphylococcal enterotoxin C1

rSEB:

recombinant staphylococcal enterotoxin B

TSST:

toxic shock syndrome toxin

FACS:

fluorescence activated cell sorter

LN:

lymph node

APC:

antigen presenting cell

3HTdR:

tritiated thymidine

PCR:

polymerase chain reaction

IL-2:

interleukin-2

BB-DR:

Biobreeding diabetes-resistant

RT1u, ConA:

concanavalin A

mAb:

monoclonal antibody

CD4 :

T-cell differentiation antigen

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Author information

Authors and Affiliations

  1. Barbara Davis Center for Childhood Diabetes, Denver, Colorado, USA

    K. S. Sellins &  D. Bellgrau

  2. San Diego Regional Cancer Center, San Diego, California, USA

    D. P. Gold

  3. Department of Immunology, University of Colorado School of Medicine, Denver, Colorado, USA

    D. Bellgrau

Authors
  1. K. S. Sellins
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  2. D. P. Gold
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  3. D. Bellgrau
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Sellins, K.S., Gold, D.P. & Bellgrau, D. Resistance to tolerance induction in the diabetes-prone Biobreeding rat as one manifestation of abnormal responses to superantigens. Diabetologia 39, 28–36 (1996). https://doi.org/10.1007/BF00400410

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  • DOI: https://doi.org/10.1007/BF00400410

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