Activated alpha beta-CD8+, but not alpha alpha-CD8+, TCR-alpha beta+ murine intestinal intraepithelial lymphocytes can mediate perforin-based cytotoxicity, whereas both subsets are active in Fas-based cytotoxicity.
CD8 single-positive (CD8+) T cells in murine intestinal intraepithelial lymphocytes (iIEL) consist of alpha alpha-CD8+ and alpha beta-CD8+ subpopulations. Cytotoxicity represents an important function of peripheral CD8+ T cells, so we examined perforin-granzymebased and Fas-based cytotoxicity of activated CD8+ TCR-alpha beta+ iIEL subsets. We found that allospecific CTL activity was induced from alpha beta-CD8+ iIEL but not from alpha alpha-CD8+ iIEL even when allospecific TCR were present on the iIEL, as demonstrated by using 2C TCR transgenic mice. On the other hand, both CD8+ iIEL subsets proliferated upon allostimulation with a lower responder frequency than CD8+ LN cells. The alpha alpha-CD8+ TCR-alpha beta+ iIEL appeared to lose their ability to perform perforin-based killing after activation through TCR because fresh cells lysed P815 cells coated with anti-TCR beta-chain (TCR-beta) mAb, whereas cells activated by plate-bound anti-TCR mAb did not. Of interest, both activated CD8+ TCR-alpha beta+ iIEL subsets, but not fresh cells, were able to mediate Fas-based killing when triggered with PMA and CA2+ ionophore.
Gelfanov
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V
Institute of Molecular Biology, Academia Sinica, Taiwan, Republic of China.
Gelfanova
V
V
Lai
Y G
YG
Liao
N S
NS
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D016130:Immunophenotyping; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D007519:Isoantigens / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000145:classification / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019014:fas Receptor / Q000276:immunology*
D000911:Antibodies, Monoclonal; D007519:Isoantigens; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D019014:fas Receptor; D054353:Perforin