Abstract
Productive immune responses require an appropriate environment to support peripheral CD8+ T cell survival. Althoug h host MHC class I molecules appear to be required for this process, the cellular and molecular requirements have not been comprehensively studied. Using adoptive transfer of 2C/recombinase-activating gene-2 (RAG-2 -/- TCR-transgenic T cells, we found that the survival of both naive and effector CD8+ T cells was dependent upon host expression of the same MHC class I alleles that supported thymic selection. Expression of appropriate MHC class I by either bone marrow- or non-bone-marrow-derived cells was sufficient, suggesting that professional antigen-presenting cells were not mandatory. In contrast to MHC class I, neither T cell expression of CD28 nor host expression of ICAM-1 was required for peripheral T cell survival. Finally, T cell death in the absence of appropriate host MHC class I was overcome by elimination of Fas signaling but not by over-expression of Bcl-XL by CD8+ T cells. These results suggest that, in the absence of a survival signal provided by engagement of host MHC/self peptide complexes, CD8+ T cells die via a Fas-dependent, mitochondria-independent pathway.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2917-2926 |
| Number of pages | 10 |
| Journal | European Journal of Immunology |
| Volume | 33 |
| Issue number | 10 |
| DOIs | |
| State | Published - Oct 2003 |
| Externally published | Yes |
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Keywords
- Apoptosis
- CD8
- MHC
- T lymphocytes
- TCR
ASJC Scopus subject areas
- Immunology
Cite this
Death of peripheral CD8+ T cells in the absence of MHC class I is Fas-dependent and not blocked by Bcl-xL. / Markiewicz, Mary A.; Brown, Ian Elliott; Gajewski, Thomas F.
In: European Journal of Immunology, Vol. 33, No. 10, 10.2003, p. 2917-2926.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Death of peripheral CD8+ T cells in the absence of MHC class I is Fas-dependent and not blocked by Bcl-xL
AU - Markiewicz, Mary A.
AU - Brown, Ian Elliott
AU - Gajewski, Thomas F.
PY - 2003/10
Y1 - 2003/10
N2 - Productive immune responses require an appropriate environment to support peripheral CD8+ T cell survival. Althoug h host MHC class I molecules appear to be required for this process, the cellular and molecular requirements have not been comprehensively studied. Using adoptive transfer of 2C/recombinase-activating gene-2 (RAG-2 -/- TCR-transgenic T cells, we found that the survival of both naive and effector CD8+ T cells was dependent upon host expression of the same MHC class I alleles that supported thymic selection. Expression of appropriate MHC class I by either bone marrow- or non-bone-marrow-derived cells was sufficient, suggesting that professional antigen-presenting cells were not mandatory. In contrast to MHC class I, neither T cell expression of CD28 nor host expression of ICAM-1 was required for peripheral T cell survival. Finally, T cell death in the absence of appropriate host MHC class I was overcome by elimination of Fas signaling but not by over-expression of Bcl-XL by CD8+ T cells. These results suggest that, in the absence of a survival signal provided by engagement of host MHC/self peptide complexes, CD8+ T cells die via a Fas-dependent, mitochondria-independent pathway.
AB - Productive immune responses require an appropriate environment to support peripheral CD8+ T cell survival. Althoug h host MHC class I molecules appear to be required for this process, the cellular and molecular requirements have not been comprehensively studied. Using adoptive transfer of 2C/recombinase-activating gene-2 (RAG-2 -/- TCR-transgenic T cells, we found that the survival of both naive and effector CD8+ T cells was dependent upon host expression of the same MHC class I alleles that supported thymic selection. Expression of appropriate MHC class I by either bone marrow- or non-bone-marrow-derived cells was sufficient, suggesting that professional antigen-presenting cells were not mandatory. In contrast to MHC class I, neither T cell expression of CD28 nor host expression of ICAM-1 was required for peripheral T cell survival. Finally, T cell death in the absence of appropriate host MHC class I was overcome by elimination of Fas signaling but not by over-expression of Bcl-XL by CD8+ T cells. These results suggest that, in the absence of a survival signal provided by engagement of host MHC/self peptide complexes, CD8+ T cells die via a Fas-dependent, mitochondria-independent pathway.
KW - Apoptosis
KW - CD8
KW - MHC
KW - T lymphocytes
KW - TCR
UR - http://www.scopus.com/inward/record.url?scp=0242350891&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0242350891&partnerID=8YFLogxK
U2 - 10.1002/eji.200324273
DO - 10.1002/eji.200324273
M3 - Article
C2 - 14515276
AN - SCOPUS:0242350891
VL - 33
SP - 2917
EP - 2926
JO - European Journal of Immunology
JF - European Journal of Immunology
SN - 0014-2980
IS - 10
ER -