Rapid killing of murine lymph node T blasts by intestinal intraepithelial lymphocytes in vitro.
We examined the effect of murine intestinal intraepithelial lymphocytes (IEL) on the proliferation of murine lymph node T cells (LN-T) in vitro. An IEL fraction prevented the proliferation of LN-T stimulated with antigen and X-irradiated spleen cells, or with anti-CD3 monoclonal antibodies (mAb). Concanavalin A-activated LN-T were less sensitive. Such an inhibitory activity was recovered from a CD8-depleted population by panning of bulk IEL using anti-CD8 alpha mAb. This population of BALB/c IEL showed less granzyme A activity, and its surface markers were positive for CD8 (4%), CD3 (80-90%), CD4 (2-6%), alpha-beta TcR (45-70%), and gamma-delta TcR (4-9%). Asialo-GM1 and Thy1.2 were variably expressed, but interleukin-2 (IL-2) receptor-alpha and Fc gamma receptor were not. By contrast, no cytotoxicity against YAC-1 was detected in a CD8-depleted IEL population by a 6-h 51Cr-release assay. Although IEL from severe-combined immunodeficient mice lacking CD4, CD8 and TcR, but expressing IL-2 receptor, showed cytotoxicity against YAC-1, their inhibitory activity against LN-T was almost the same as that by IEL from BALB/c mice. When LN-T blasts (greater than 75% CD4+) activated with anti-CD3 were treated with CD8-depleted IEL, intact cellular DNA of the T blasts disappeared within 1 h with increased amounts of small-sized DNA. These results suggest that CD8- IEL directly and nonspecifically kill lymph node CD4+ T blasts and possibly down-regulate TcR-mediated proliferation of peripheral T cells in the gut epithelium.
Kawamoto
Y
Y
Department of Microbiology, Fujita Health University School of Medicine, Aichi, Japan.
Sasaki
K
K
Kato
Y
Y
Kojima
K
K
Tsuji
T
T
Miyama
A
A
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D004249:DNA Damage / Q000276:immunology; D004847:Epithelial Cells; D004848:Epithelium / Q000276:immunology; D005260:Female; D007108:Immune Tolerance; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation / Q000235:genetics; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism