Anergic T lymphocytes selectively express an integrin regulatory protein of the cytohesin family.
It has been proposed that the maintenance of T cell anergy depends on the induction of negative regulatory factors. Differential display of reverse transcribed RNA was used to identify novel genes that might mediate this function in anergic Th1 clones. We report that anergic Th1 clones do indeed express a genetic program different from that of responsive T cells. Moreover, one gene, the general receptor of phosphoinositides 1 (GRP1), was selectively induced in anergic T cells. The GRP1, located in the plasma membrane, regulated integrin-mediated adhesion and was invariably associated with unresponsiveness in multiple models of anergy. T cells expressing retrovirally transduced GRP1 exhibited normal proliferation and cytokine production. However, GRP1-transduced T cells were not stable and rapidly lost GRP1 expression. Thus, although GRP1 may not directly mediate T cell anergy, it regulates cell expansion and survival, perhaps through its integrin-associated activities.
Korthäuer
U
U
Ben May Institute for Cancer Research, University of Chicago, IL 60637, USA.
Nagel
W
W
Davis
E M
EM
Le Beau
M M
MM
Menon
R S
RS
Mitchell
E O
EO
Kozak
C A
CA
Kolanus
W
W
Bluestone
J A
JA
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D017252:CD3 Complex / Q000276:immunology; D002448:Cell Adhesion / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D002874:Chromosome Mapping; D017635:Clonal Anergy / Q000235:genetics; D002999:Clone Cells; D005786:Gene Expression Regulation / Q000276:immunology; D020662:Guanine Nucleotide Exchange Factors; D016023:Integrins / Q000502:physiology*; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D051379:Mice; D008805:Mice, Inbred A; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010716:Phosphatidylinositols / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis* / Q000235:genetics / Q000302:isolation & purification; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D014162:Transfection
D000906:Antibodies; D017252:CD3 Complex; D015815:Cell Adhesion Molecules; D020662:Guanine Nucleotide Exchange Factors; D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; D010716:Phosphatidylinositols; D011948:Receptors, Antigen, T-Cell; D018160:Receptors, Cytoplasmic and Nuclear; C100723:cytohesin-1; C040985:phosphatidylinositol receptors; D018799:Intercellular Adhesion Molecule-1