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Class I-restricted cross-presentation of exogenous self-antigens leads to deletion of autoreactive CD8(+) T cells.

Kurts C, Kosaka H, Carbone FR, Miller JF, Heath WR - J. Exp. Med. (1997)

Bottom Line: Here, we show that adoptively transferred or thymically derived OT-I cells activated by cross-presentation are deleted from the peripheral pool of recirculating lymphocytes.Such deletion only required antigen recognition on a bone marrow-derived population, suggesting that cells of the professional APC class may be tolerogenic under these circumstances.Our results provide a mechanism by which the immune system can induce CD8(+) T cell tolerance to autoantigens that are expressed outside the recirculation pathway of naive T cells.

View Article: PubMed Central - PubMed

Affiliation: Thymus Biology Unit, The Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Parkville 3050, Victoria, Australia.

ABSTRACT
In this report, we show that cross-presentation of self-antigens can lead to the peripheral deletion of autoreactive CD8(+) T cells. We had previously shown that transfer of ovalbumin (OVA)-specific CD8(+) T cells (OT-I cells) into rat insulin promoter-membrane-bound form of OVA transgenic mice, which express the model autoantigen OVA in the proximal tubular cells of the kidneys, the beta cells of the pancreas, the thymus, and the testis of male mice, led to the activation of OT-I cells in the draining lymph nodes. This was due to class I-restricted cross-presentation of exogenous OVA on a bone marrow-derived antigen presenting cell (APC) population. Here, we show that adoptively transferred or thymically derived OT-I cells activated by cross-presentation are deleted from the peripheral pool of recirculating lymphocytes. Such deletion only required antigen recognition on a bone marrow-derived population, suggesting that cells of the professional APC class may be tolerogenic under these circumstances. Our results provide a mechanism by which the immune system can induce CD8(+) T cell tolerance to autoantigens that are expressed outside the recirculation pathway of naive T cells.

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Related in: MedlinePlus

Bone marrow–derived APC activate OT-I cells in the draining LN of RIP–mOVA mice. 5 × 106 CFSE labeled OT-I cells were  transferred into RIP–mOVA mice backcrossed to B6 (A, B, E, F) or bm1  (C, D, G, H) and grafted with B6 (A, C, E, G) or bm1 (B, D, F, H) bone  marrow. After 3 d, renal (A–D) and inguinal (E–H) lymph node cells  were examined by flow cytometry. Profiles were gated for CD8+ cells.
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Figure 2: Bone marrow–derived APC activate OT-I cells in the draining LN of RIP–mOVA mice. 5 × 106 CFSE labeled OT-I cells were transferred into RIP–mOVA mice backcrossed to B6 (A, B, E, F) or bm1 (C, D, G, H) and grafted with B6 (A, C, E, G) or bm1 (B, D, F, H) bone marrow. After 3 d, renal (A–D) and inguinal (E–H) lymph node cells were examined by flow cytometry. Profiles were gated for CD8+ cells.

Mentions: Using the above technique, divided cells were first apparent at 25 h after transfer (data not shown). After 43 h, some OT-I cells had divided four times (Fig. 1), six times within 52 h (data not shown), greater than eight times within 68 h (Fig. 2). Therefore, one cell cycle required ∼4.5 h in vivo.


Class I-restricted cross-presentation of exogenous self-antigens leads to deletion of autoreactive CD8(+) T cells.

Kurts C, Kosaka H, Carbone FR, Miller JF, Heath WR - J. Exp. Med. (1997)

Bone marrow–derived APC activate OT-I cells in the draining LN of RIP–mOVA mice. 5 × 106 CFSE labeled OT-I cells were  transferred into RIP–mOVA mice backcrossed to B6 (A, B, E, F) or bm1  (C, D, G, H) and grafted with B6 (A, C, E, G) or bm1 (B, D, F, H) bone  marrow. After 3 d, renal (A–D) and inguinal (E–H) lymph node cells  were examined by flow cytometry. Profiles were gated for CD8+ cells.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2198972&req=5

Figure 2: Bone marrow–derived APC activate OT-I cells in the draining LN of RIP–mOVA mice. 5 × 106 CFSE labeled OT-I cells were transferred into RIP–mOVA mice backcrossed to B6 (A, B, E, F) or bm1 (C, D, G, H) and grafted with B6 (A, C, E, G) or bm1 (B, D, F, H) bone marrow. After 3 d, renal (A–D) and inguinal (E–H) lymph node cells were examined by flow cytometry. Profiles were gated for CD8+ cells.
Mentions: Using the above technique, divided cells were first apparent at 25 h after transfer (data not shown). After 43 h, some OT-I cells had divided four times (Fig. 1), six times within 52 h (data not shown), greater than eight times within 68 h (Fig. 2). Therefore, one cell cycle required ∼4.5 h in vivo.

Bottom Line: Here, we show that adoptively transferred or thymically derived OT-I cells activated by cross-presentation are deleted from the peripheral pool of recirculating lymphocytes.Such deletion only required antigen recognition on a bone marrow-derived population, suggesting that cells of the professional APC class may be tolerogenic under these circumstances.Our results provide a mechanism by which the immune system can induce CD8(+) T cell tolerance to autoantigens that are expressed outside the recirculation pathway of naive T cells.

View Article: PubMed Central - PubMed

Affiliation: Thymus Biology Unit, The Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Parkville 3050, Victoria, Australia.

ABSTRACT
In this report, we show that cross-presentation of self-antigens can lead to the peripheral deletion of autoreactive CD8(+) T cells. We had previously shown that transfer of ovalbumin (OVA)-specific CD8(+) T cells (OT-I cells) into rat insulin promoter-membrane-bound form of OVA transgenic mice, which express the model autoantigen OVA in the proximal tubular cells of the kidneys, the beta cells of the pancreas, the thymus, and the testis of male mice, led to the activation of OT-I cells in the draining lymph nodes. This was due to class I-restricted cross-presentation of exogenous OVA on a bone marrow-derived antigen presenting cell (APC) population. Here, we show that adoptively transferred or thymically derived OT-I cells activated by cross-presentation are deleted from the peripheral pool of recirculating lymphocytes. Such deletion only required antigen recognition on a bone marrow-derived population, suggesting that cells of the professional APC class may be tolerogenic under these circumstances. Our results provide a mechanism by which the immune system can induce CD8(+) T cell tolerance to autoantigens that are expressed outside the recirculation pathway of naive T cells.

Show MeSH
Related in: MedlinePlus