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CD4+ T cell help impairs CD8+ T cell deletion induced by cross-presentation of self-antigens and favors autoimmunity.

Kurts C, Carbone FR, Barnden M, Blanas E, Allison J, Heath WR, Miller JF - J. Exp. Med. (1997)

Bottom Line: Such cross-presentation of self-antigens leads to CD8+ T cell tolerance induction via deletion.Analysis of the fate of CD8+ T cells indicated that CD4(+) T cell help impaired their deletion.These data indicate that control of such help is critical for the maintenance of CD8+ T cell tolerance induced by cross-presentation.

View Article: PubMed Central - PubMed

Affiliation: Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Victoria 3050, Australia.

ABSTRACT
Self-antigens expressed in extrathymic tissues such as the pancreas can be transported to draining lymph nodes and presented in a class I-restricted manner by bone marrow-derived antigen-presenting cells. Such cross-presentation of self-antigens leads to CD8+ T cell tolerance induction via deletion. In this report, we investigate the influence of CD4+ T cell help on this process. Small numbers of autoreactive OVA-specific CD8+ T cells were unable to cause diabetes when adoptively transferred into mice expressing ovalbumin in the pancreatic beta cells. Coinjection of OVA-specific CD4+ helper T cells, however, led to diabetes in a large proportion of mice (68%), suggesting that provision of help favored induction of autoimmunity. Analysis of the fate of CD8+ T cells indicated that CD4(+) T cell help impaired their deletion. These data indicate that control of such help is critical for the maintenance of CD8+ T cell tolerance induced by cross-presentation.

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Related in: MedlinePlus

Islet infiltration in  RIP-mOVA recipients of OT-I  and OT-II cells. The following  numbers of OT-I and OT-II  cells were adoptively transferred  into unirradiated RIP-mOVA  mice. (A) 5 × 106 OT-I cells;  (B) 0.25 × 106 OT-I cells + 2 ×  106 OT-II cells; (C) 1 × 106  OT-I cells; (D) 10 × 106 OT-II  cells. Sections of the pancreas  were stained 5 (A, B, and D) or 8 d  (C) after adoptive transfer for  CD8 (A–C) or CD4 (D). Arrows in C indicate infiltrating  CD8+ cells.
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Figure 1: Islet infiltration in RIP-mOVA recipients of OT-I and OT-II cells. The following numbers of OT-I and OT-II cells were adoptively transferred into unirradiated RIP-mOVA mice. (A) 5 × 106 OT-I cells; (B) 0.25 × 106 OT-I cells + 2 × 106 OT-II cells; (C) 1 × 106 OT-I cells; (D) 10 × 106 OT-II cells. Sections of the pancreas were stained 5 (A, B, and D) or 8 d (C) after adoptive transfer for CD8 (A–C) or CD4 (D). Arrows in C indicate infiltrating CD8+ cells.

Mentions: Histological examination revealed that on day 5 after adoptive transfer of 5 × 106 OT-I cells, the pancreatic islets of RIP-mOVA recipients were densely infiltrated with CD8+ T cells (Fig. 1 A) and with CD4+ T cells, B cells, and MAC-1–positive cells, which were of host origin (data not shown). Recipients of 1 × 106 OT-I cells that did not develop diabetes showed some CD8+ T cells within the islets on day 8 (Fig. 1 C), whereas recipients of less OT-I cells showed only sporadic islet infiltration (data not shown).


CD4+ T cell help impairs CD8+ T cell deletion induced by cross-presentation of self-antigens and favors autoimmunity.

Kurts C, Carbone FR, Barnden M, Blanas E, Allison J, Heath WR, Miller JF - J. Exp. Med. (1997)

Islet infiltration in  RIP-mOVA recipients of OT-I  and OT-II cells. The following  numbers of OT-I and OT-II  cells were adoptively transferred  into unirradiated RIP-mOVA  mice. (A) 5 × 106 OT-I cells;  (B) 0.25 × 106 OT-I cells + 2 ×  106 OT-II cells; (C) 1 × 106  OT-I cells; (D) 10 × 106 OT-II  cells. Sections of the pancreas  were stained 5 (A, B, and D) or 8 d  (C) after adoptive transfer for  CD8 (A–C) or CD4 (D). Arrows in C indicate infiltrating  CD8+ cells.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2199175&req=5

Figure 1: Islet infiltration in RIP-mOVA recipients of OT-I and OT-II cells. The following numbers of OT-I and OT-II cells were adoptively transferred into unirradiated RIP-mOVA mice. (A) 5 × 106 OT-I cells; (B) 0.25 × 106 OT-I cells + 2 × 106 OT-II cells; (C) 1 × 106 OT-I cells; (D) 10 × 106 OT-II cells. Sections of the pancreas were stained 5 (A, B, and D) or 8 d (C) after adoptive transfer for CD8 (A–C) or CD4 (D). Arrows in C indicate infiltrating CD8+ cells.
Mentions: Histological examination revealed that on day 5 after adoptive transfer of 5 × 106 OT-I cells, the pancreatic islets of RIP-mOVA recipients were densely infiltrated with CD8+ T cells (Fig. 1 A) and with CD4+ T cells, B cells, and MAC-1–positive cells, which were of host origin (data not shown). Recipients of 1 × 106 OT-I cells that did not develop diabetes showed some CD8+ T cells within the islets on day 8 (Fig. 1 C), whereas recipients of less OT-I cells showed only sporadic islet infiltration (data not shown).

Bottom Line: Such cross-presentation of self-antigens leads to CD8+ T cell tolerance induction via deletion.Analysis of the fate of CD8+ T cells indicated that CD4(+) T cell help impaired their deletion.These data indicate that control of such help is critical for the maintenance of CD8+ T cell tolerance induced by cross-presentation.

View Article: PubMed Central - PubMed

Affiliation: Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Victoria 3050, Australia.

ABSTRACT
Self-antigens expressed in extrathymic tissues such as the pancreas can be transported to draining lymph nodes and presented in a class I-restricted manner by bone marrow-derived antigen-presenting cells. Such cross-presentation of self-antigens leads to CD8+ T cell tolerance induction via deletion. In this report, we investigate the influence of CD4+ T cell help on this process. Small numbers of autoreactive OVA-specific CD8+ T cells were unable to cause diabetes when adoptively transferred into mice expressing ovalbumin in the pancreatic beta cells. Coinjection of OVA-specific CD4+ helper T cells, however, led to diabetes in a large proportion of mice (68%), suggesting that provision of help favored induction of autoimmunity. Analysis of the fate of CD8+ T cells indicated that CD4(+) T cell help impaired their deletion. These data indicate that control of such help is critical for the maintenance of CD8+ T cell tolerance induced by cross-presentation.

Show MeSH
Related in: MedlinePlus