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An affinity/avidity model of peripheral T cell regulation
Hong Jiang, … , Itamar Goldstein, Leonard Chess
Hong Jiang, … , Itamar Goldstein, Leonard Chess
Published February 1, 2005
Citation Information: J Clin Invest. 2005;115(2):302-312. https://doi.org/10.1172/JCI23879.
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Article Immunology

An affinity/avidity model of peripheral T cell regulation

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Abstract

We show in these studies that Qa-1–dependent CD8+ T cells are involved in the establishment and maintenance of peripheral self tolerance as well as facilitating affinity maturation of CD4+ T cells responding to foreign antigen. We provide experimental evidence that the strategy used by the Qa-1–dependent CD8+ T cells to accomplish both these tasks in vivo is to selectively downregulate T cell clones that respond to both self and foreign antigens with intermediate, not high or low, affinity/avidity. Thus, the immune system evolved to regulate peripheral immunity using a unified mechanism that efficiently and effectively permits the system to safeguard peripheral self tolerance yet promote the capacity to deal with foreign invaders.

Authors

Hong Jiang, Yilun Wu, Bitao Liang, Zongyu Zheng, Guomei Tang, Jean Kanellopoulos, Mark Soloski, Robert Winchester, Itamar Goldstein, Leonard Chess

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Figure 1

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Qa-1–dependent CD8+ T cells are involved in the establishment and mainte...
Qa-1–dependent CD8+ T cells are involved in the establishment and maintenance of peripheral self tolerance to HEL in HEL Tg mice. (A) The unresponsiveness to HEL in HEL high Tg mice could be broken by treatment with anti-CD8 and anti–Qa-1 mAbs. HEL immunization and in vivo mAb treatment were performed and CD4+ T cells were purified from pooled draining lymph node cells from different groups of mice and assayed in a T cell proliferation assay as described in Methods. Data are representative of 4 separate experiments with 2–4 mice per group. (B) CD8+ T cells regulate immune response to self antigen HEL in HEL low Tg mice. Experiments were performed as described in Methods. Data are representative of 6 separate experiments with 2–4 mice per group. (C) CD8+ T cells downregulate the primary immune responses to HEL in HEL low Tg mice when adoptively transferred. CD8+ T cells were injected i.v. into recipient mice, and the mice were immunized with HEL 1 day later. The CD4+ T cells were isolated from pooled lymph node cells of recipient mice 7–9 days after the immunization, and T cell proliferation assays were performed. Data are representative of 4 separate experiments with 2–4 mice per group. Control, no transfer; n/LTg, CD8+ T cells transferred from naive HEL low Tg mice; HEL/LTg, CD8+ T cells transferred from 2– HEL-immunized HEL low Tg mice; n/HTg, CD8+ T cells transferred from naive HEL high Tg mice; HEL/HTg, CD8+ T cells transferred from 1– HEL-immunized HEL high Tg mice. 3HTdr, 3H-thymidine.
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