Lymphokine-activated killing by human intestinal lymphocytes

Area of Science:

• Immunology
• Gastroenterology
• Oncology

Background:

• Human intraepithelial lymphocytes (IEL) are CD8+ T cells in the gut lining.
• IEL are hypothesized to be the first line of defense against colon cancers.
• Lymphokine-activated killer (LAK) cells are cytotoxic lymphocytes activated by interleukin-2 (IL-2).

Purpose of the Study:

• To evaluate the LAK activity of human IEL.
• To compare IEL LAK activity with that of lamina propria lymphocytes (LPL).
• To determine the phenotypes of precursor and effector LAK cells within IEL and LPL.

Main Methods:

• Phenotyping of IEL and LPL by antibody and complement lysis before and after IL-2 culture.
• Measurement of changes in lytic activity against target cells.
• Analysis of IEL LAK activity against DLD-1 (colonic adenocarcinoma) and K-562 (leukemia) cells.

Main Results:

• IEL LAK precursor and effector cells comprised mixed populations expressing CD2, CD3, CD8, and NKH1.
• LPL LAK activity involved CD2+CD3+CD4-CD8- precursor cells and CD8+ effector cells.
• IEL LAK activity against DLD-1 cells was inhibited by antibodies to CD2, CD11a, and HML-1; against K-562 cells by CD2, CD11a, and CD54, but not HML-1.

Conclusions:

• IEL mediate LAK activity via a heterogeneous cell population, unlike LPL which utilize distinct precursor and effector cells.
• The same effector LAK IEL can kill both DLD-1 and K-562 target cells.
• Different molecular mechanisms mediate IEL LAK cell cytotoxicity against distinct target cells, indicating target-specific interactions.