Mechanisms of tolerance induction: splenocytes from total lymphoid irradiated mice inhibit the IL-2 pathway in TCR-activated CD4 cells

Elizabeth H Field; Zhong-Xiang Ye; Todd M Rouse

doi:10.4049/jimmunol.157.9.3796

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Mechanisms of tolerance induction: splenocytes from total lymphoid irradiated mice inhibit the IL-2 pathway in TCR-activated CD4 cells

Journal article

Peer reviewed

Mechanisms of tolerance induction: splenocytes from total lymphoid irradiated mice inhibit the IL-2 pathway in TCR-activated CD4 cells

Elizabeth H Field, Zhong-Xiang Ye and Todd M Rouse

The Journal of immunology (1950), Vol.157(9), pp.3796-3803

11/01/1996

DOI: 10.4049/jimmunol.157.9.3796

PMID: 8892608

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Abstract

Mice given total lymphoid irradiation (TLI) can be tolerized by an incompletely understood mechanism to foreign Ags given during a brief window of time immediately after completing radiation. We previously showed that splenocytes taken from mice immediately after completing TLI treatment (TLI cells) block the ability of control cells to proliferate or to produce IL-2 in response to alloantigen, suggesting that TLI cells interfere with the IL-2 pathway in responder lymphocytes. To further characterize the mechanism by which TLI cells affect IL-2, we utilized an in vitro system of T cell activation. Adding TLI cells into cultures decreased the ability of TCR-stimulated T cells to proliferate and to secrete IL-2 by 40 to 60%. Exogenous IL-2 did not restore the proliferative response. The inhibition of IL-2 secretion resulted both from a decrease in the number of IL-2-producing cells and a decrease in IL-2 mRNA transcription. TLI cells directly inhibited IL-2 secretion by TCR-stimulated CD4 cells, as determined by ELISPOT. Competitive PCR demonstrated that TLI cells decreased IL-2 transcription of TCR-stimulated CD4 cells by 75%. In situ hybridization confirmed that unfractionated spleen and sorted CD4 cells from TCR-stimulated cultures transcribed less IL-2 RNA in the presence of TLI cells. The results show that TLI cells directly inhibit IL-2 transcription and protein secretion of normal TCR-stimulated CD4 cells.

T-Lymphocyte Subsets - immunology

Spleen - immunology

Immunosuppression - methods

Mice, Inbred A

Coculture Techniques

Adoptive Transfer

Th1 Cells - immunology

Th1 Cells - metabolism

RNA, Messenger - biosynthesis

Immune Tolerance - immunology

Female

Receptors, Antigen, T-Cell - immunology

Th1 Cells - drug effects

Gene Expression Regulation

T-Lymphocyte Subsets - radiation effects

CD4 Lymphocyte Count

Spleen - cytology

Lymphatic Irradiation

T-Lymphocyte Subsets - transplantation

Interleukin-2 - genetics

Animals

Lymphocyte Activation - drug effects

Interleukin-2 - pharmacology

Mice

Mice, Inbred BALB C

Th1 Cells - secretion

Interleukin-2 - biosynthesis

Interleukin-2 - secretion

Details

Title: Subtitle: Mechanisms of tolerance induction: splenocytes from total lymphoid irradiated mice inhibit the IL-2 pathway in TCR-activated CD4 cells
Creators: Elizabeth H Field - Department of Veterans Affairs Medical Center, Iowa City, IA 52246, USA
Zhong-Xiang Ye
Todd M Rouse
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.157(9), pp.3796-3803
DOI: 10.4049/jimmunol.157.9.3796
PMID: 8892608
ISSN: 0022-1767
eISSN: 1550-6606
Grant note: DK25295 / NIDDK NIH HHS CA45541 / NCI NIH HHS
Language: English
Date published: 11/01/1996
Academic Unit: Immunology; Internal Medicine
Record Identifier: 9984094772302771

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