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Human small intestinal mucosa harbours a small population of cytolytically active CD8 + αβ T lymphocytes
Author(s) -
Melgar Silvia,
Bas Anna,
Hammarström Sten,
Hammarström MarieLouise
Publication year - 2002
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.2002.01461.x
Subject(s) - perforin , biology , granzyme , microbiology and biotechnology , fas ligand , cytotoxic t cell , granzyme b , cytotoxicity , cd8 , intraepithelial lymphocyte , t cell receptor , cd3 , t cell , apoptosis , immunology , immune system , programmed cell death , in vitro , biochemistry
Summary Intraepithelial lymphocytes (IEL) in normal human small intestine exhibit cytotoxicity. This study was undertaken to characterize the effector cells and their mode of action. Freshly isolated jejunal IEL and lamina propria lymphocytes (LPL), as well as IEL and LPL depleted of CD4 + , CD8 + and T‐cell receptor (TCR)‐γδ + cells were used as effector cells in anti‐CD3‐mediated redirected cytotoxicity against a murine FcγR‐expressing cell line. Effector cell frequencies were estimated by effector to target cell titration and limiting dilution. The capacity of IEL and LPL to kill a Fas‐expressing human T‐cell line was also analysed. T‐cell subsets were analysed for perforin, granzyme B, Fas‐ligand (FasL), tumour necrosis factor‐α (TNF‐α) and TNF‐related apoptosis inducing ligand (TRAIL) mRNA expression by reverse transcription–polymerase chain reaction (RT‐PCR). Frequencies of IEL expressing the perforin and FasL proteins were determined by immunomorphometry. Both IEL and LPL exhibited significant Ca 2+ ‐dependent, anti‐CD3‐mediated cytotoxicity, ≈ 30% specific lysis at the effector to target cell ratio 100. The cytotoxic cells constituted, however, only a small fraction of IEL and LPL (≈ 0·01%). CD8 + TCR‐αβ + cells accounted for virtually all the cytotoxicity and expressed mRNA for all five cytotoxic proteins. The frequency of granzyme B‐expressing samples was higher in CD8 + cells than in CD4 + cells ( P <0·05 and <0·01 for IEL and LPL, respectively). In addition, both IEL and LPL exhibited significant spontaneous anti‐CD3‐independent cytotoxicity against Fas‐expressing human T cells. This killing was mediated by Fas–FasL interaction. On average, 2–3% of the IEL expressed perforin and FasL. We speculate that CD8 + memory cells accumulate in the jejunal mucosa and that the CD8 + TCR‐αβ + lymphocytes executing TCR/CD3‐mediated, Ca 2+ ‐dependent cytotoxicity are classical cytotoxic T lymphocytes ‘caught in the act’ of eliminating infected epithelial cells through perforin/granzyme exocytosis. The observed Fas/FasL‐mediated cytotoxicity may be a reflection of ongoing down‐regulation of local immune responses by ‘activation‐induced cell death’.