Elevated expression of Bcl-2 and Bcl-x by intestinal intraepithelial lymphocytes: resistance to apoptosis by glucocorticoids and irradiation.
Administration of glucocorticoids or exposure to ionizing radiation in vivo results in a rapid cell death of thymocytes. We report that murine small intestinal intraepithelial lymphocytes (IEL) are resistant to both steroid- and radiation-induced deletion. This is due to resistance to apoptosis, as evidenced by the absence of detectable apoptotic IEL nuclei in situ after in vivo glucocorticoid treatment. IEL express normal levels of glucocorticoid receptors and these receptors bind [3H]dexamethasone to equivalent levels as other lymphocyte populations. Thus, their survival is due to post-receptor signaling mechanisms. Many IEL express high levels of Bcl-2 and that of these Bcl-2high IEL are largely TCR gamma delta +. Those IEL that do express high levels of Bcl-2 are CD8 alpha + beta - CD4-. In addition, IEL express Bcl-x, another protein shown to be involved in the protection of cells from apoptotic signals. IEL represent the first lymphocyte population in vivo shown to have high levels of expression of both molecules, that otherwise occur only in activated lymphocytes in vitro. These data suggest that the Bcl-2+Bcl-x+ IEL are activated cells and not an effete population of cells necessarily destined to die. Also, the high levels of Bcl-2 and Bcl-x in this in vivo activated population supports the in vitro correlate of protection from activation-induced cell death.
Van Houten
N
N
Department of Internal Medicine, University of Texas Medical Branch, Galveston 77555, USA.
Blake
S F
SF
Li
E J
EJ
Hallam
T A
TA
Chilton
D G
DG
Gourley
W K
WK
Boise
L H
LH
Thompson
C B
CB
Thompson
E B
EB
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology / Q000528:radiation effects*; D015704:CD4 Antigens; D016827:CD8 Antigens; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D006854:Hydrocortisone / Q000494:pharmacology; D016130:Immunophenotyping; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000276:immunology / Q000528:radiation effects*; D007421:Intestine, Small / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D008024:Ligands; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D018655:Lymphocyte Count / Q000187:drug effects / Q000528:radiation effects; D051379:Mice; D008808:Mice, Inbred CBA; D010581:Peyer's Patches / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000502:physiology; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011965:Receptors, Glucocorticoid / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D013950:Thymus Gland / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D051020:bcl-X Protein
C494812:Bcl2l1 protein, mouse; D015704:CD4 Antigens; D016827:CD8 Antigens; D005938:Glucocorticoids; D008024:Ligands; D019253:Proto-Oncogene Proteins c-bcl-2; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011965:Receptors, Glucocorticoid; D051020:bcl-X Protein; D003907:Dexamethasone; D006854:Hydrocortisone