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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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Analysis of the activation status of OT-I cells in TG-RIP  mice. Expression of CD69 (A–C) and L-selectin (D–F) by Vα2+ lymphocytes from the peripheral LN of TG-nontransgenic mice (A and D)  and the peripheral (B and E) and renal (C and F) LN of TG-RIP mice.
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Figure 5: Analysis of the activation status of OT-I cells in TG-RIP mice. Expression of CD69 (A–C) and L-selectin (D–F) by Vα2+ lymphocytes from the peripheral LN of TG-nontransgenic mice (A and D) and the peripheral (B and E) and renal (C and F) LN of TG-RIP mice.

Mentions: Consistent with an active deletional process occurring in these mice, OT-I cells from the peripheral lymphatic tissues of TG-RIP mice expressed elevated levels of the activation marker CD69 (Fig. 5, A–C) and decreased levels of L-selectin (Fig. 5, D–F) relative to that seen in TG-nontransgenic control mice. The proportion of activated OT-I cells was even higher in the lymph nodes draining OVA-expressing tissues (Fig. 5, C and F), suggesting that activation of OT-I cells in TG-RIP mice also occurred in these draining lymph nodes, presumably by the same cross-presentation mechanism that activates adoptively transferred OT-I cells.


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)

Analysis of the activation status of OT-I cells in TG-RIP  mice. Expression of CD69 (A–C) and L-selectin (D–F) by Vα2+ lymphocytes from the peripheral LN of TG-nontransgenic mice (A and D)  and the peripheral (B and E) and renal (C and F) LN of TG-RIP mice.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 5: Analysis of the activation status of OT-I cells in TG-RIP mice. Expression of CD69 (A–C) and L-selectin (D–F) by Vα2+ lymphocytes from the peripheral LN of TG-nontransgenic mice (A and D) and the peripheral (B and E) and renal (C and F) LN of TG-RIP mice.
Mentions: Consistent with an active deletional process occurring in these mice, OT-I cells from the peripheral lymphatic tissues of TG-RIP mice expressed elevated levels of the activation marker CD69 (Fig. 5, A–C) and decreased levels of L-selectin (Fig. 5, D–F) relative to that seen in TG-nontransgenic control mice. The proportion of activated OT-I cells was even higher in the lymph nodes draining OVA-expressing tissues (Fig. 5, C and F), suggesting that activation of OT-I cells in TG-RIP mice also occurred in these draining lymph nodes, presumably by the same cross-presentation mechanism that activates adoptively transferred OT-I cells.

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