GAMMA-DELTA-T-CELLS DIFFERENTIATE INTO A FUNCTIONAL BUT NONPROLIFERATIVE STATE DURING A NORMAL IMMUNE-RESPONSE

被引:35
作者
SPANER, D
MIGITA, K
OCHI, A
SHANNON, J
MILLER, RG
PEREIRA, P
TONEGAWA, S
PHILLIPS, RA
机构
[1] UNIV TORONTO,DEPT IMMUNOL,TORONTO M5G 1X8,ON,CANADA
[2] UNIV TORONTO,DEPT MED BIOPHYS,TORONTO M5G 1X8,ON,CANADA
[3] MT SINAI HOSP,SAMUEL LUNENFELD RES INST,TORONTO M5G 1X5,ONTARIO,CANADA
[4] ONTARIO CANC INST,TORONTO M4X 1K9,ONTARIO,CANADA
[5] MIT,HOWARD HUGHES MED INST,CAMBRIDGE,MA 02139
[6] MIT,CTR CANC RES,CAMBRIDGE,MA 02139
[7] MIT,DEPT BIOL,CAMBRIDGE,MA 02139
关键词
D O I
10.1073/pnas.90.18.8415
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
To obtain a homogeneous population of gammadelta T cells to investigate their role in an immune response, we have made a scid mouse doubly transgenic for rearranged gamma and delta genes. The receptor (KN6) encoded by these genes is specific for the major histocompatibility complex class I protein encoded by the T22b gene. This mouse contains high levels of transgenic gammadelta T cells in the spleen and thymus and no other T lymphocytes. Immunization of these KN6-scid (H-2d, TL(d)) mice with 10(7) C57BL/6J (abbreviated B6) (H-2b, TL(b)) Spleen cells resulted in proliferation and activation of the gammadelta T cells in spleen and clearing of the allogeneic B6 lymphocytes. Subsequently, the majority of activated cells died by apoptosis and the remaining cells were anergic with regard to proliferation. The anergic cells did not respond to restimulation by B6 spleen cells in vitro or in vivo, and addition of exogenous interleukin 2 failed to restore the response to B6 cells. Cytotoxicity, a property of KN6+ cells during a primary stimulation, was no longer detectable in the proliferatively anergic cells. However, B6 spleen cells injected into mice primed 12 days previously were cleared with a much greater efficiency than on primary challenge and in an antigen-specific manner. We conclude that after exposure to antigen, gammadelta T cells rapidly proliferate into blasts; the majority of the blasts rapidly die, with the nonproliferating cells remaining in a highly active state for several weeks and able to initiate elimination of lymphoid cells bearing the TL(b) epitope.
引用
收藏
页码:8415 / 8419
页数:5
相关论文
共 32 条
[1]   PROLIFERATIVE T-CELL ANERGY TO MLS-1A DOES NOT CORRELATE WITH INVIVO TOLERANCE [J].
BANDEIRA, A ;
MENGEL, J ;
BURLENDEFRANOUX, O ;
COUTINHO, A .
INTERNATIONAL IMMUNOLOGY, 1991, 3 (09) :923-931
[2]   RECOGNITION OF A SELF MAJOR HISTOCOMPATIBILITY COMPLEX TL REGION PRODUCT BY GAMMA-DELTA T-CELL RECEPTORS [J].
BONNEVILLE, M ;
ITO, K ;
KRECKO, EG ;
ITOHARA, S ;
KAPPES, D ;
ISHIDA, I ;
KANAGAWA, O ;
JANEWAY, CA ;
MURPHY, DB ;
TONEGAWA, S .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (15) :5928-5932
[3]   SELF-TOLERANCE TO TRANSGENIC-GAMMA-DELTA-T-CELLS BY INTRATHYMIC INACTIVATION [J].
BONNEVILLE, M ;
ISHIDA, I ;
ITOHARA, S ;
VERBEEK, S ;
BERNS, A ;
KANAGAWA, O ;
HAAS, W ;
TONEGAWA, S .
NATURE, 1990, 344 (6262) :163-165
[4]   TRANSGENIC MICE DEMONSTRATE THAT EPITHELIAL HOMING OF GAMMA-DELTA-T-CELLS IS DETERMINED BY CELL LINEAGES INDEPENDENT OF T-CELL RECEPTOR SPECIFICITY [J].
BONNEVILLE, M ;
ITOHARA, S ;
KRECKO, EG ;
MOMBAERTS, P ;
ISHIDA, I ;
KATSUKI, M ;
BERNS, A ;
FARR, AG ;
JANEWAY, CA ;
TONEGAWA, S .
JOURNAL OF EXPERIMENTAL MEDICINE, 1990, 171 (04) :1015-1026
[5]   A SEVERE COMBINED IMMUNODEFICIENCY MUTATION IN THE MOUSE [J].
BOSMA, GC ;
CUSTER, RP ;
BOSMA, MJ .
NATURE, 1983, 301 (5900) :527-530
[6]   STIMULATION BY SUPERANTIGEN [J].
COHEN, JJ ;
DUKE, RC ;
SELLINS, KS .
NATURE, 1991, 352 (6332) :199-200
[7]   RESPONSE OF T-CELLS TO HISTOCOMPATIBILITY-2 ANTIGENS - DOSE-RESPONSE KINETICS [J].
GERSHON, RK ;
LIEBHABER, SA .
JOURNAL OF EXPERIMENTAL MEDICINE, 1972, 136 (01) :112-+
[8]   RECOGNITION OF THE PRODUCT OF A NOVEL MHC TL REGION GENE (27B) BY A MOUSE GAMMA-DELTA-T-CELL RECEPTOR [J].
ITO, K ;
VANKAER, L ;
BONNEVILLE, M ;
HSU, S ;
MURPHY, DB ;
TONEGAWA, S .
CELL, 1990, 62 (03) :549-561
[9]   MONOCLONAL-ANTIBODIES SPECIFIC TO NATIVE MURINE T-CELL RECEPTOR-GAMMA-DELTA - ANALYSIS OF GAMMA-DELTA-T-CELLS DURING THYMIC ONTOGENY AND IN PERIPHERAL LYMPHOID ORGANS [J].
ITOHARA, S ;
NAKANISHI, N ;
KANAGAWA, O ;
KUBO, R ;
TONEGAWA, S .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (13) :5094-5098
[10]   HOMING OF A GAMMA-DELTA THYMOCYTE SUBSET WITH HOMOGENEOUS T-CELL RECEPTORS TO MUCOSAL EPITHELIA [J].
ITOHARA, S ;
FARR, AG ;
LAFAILLE, JJ ;
BONNEVILLE, M ;
TAKAGAKI, Y ;
HAAS, W ;
TONEGAWA, S .
NATURE, 1990, 343 (6260) :754-757