PMID- 10432285
OWN - NLM
STAT- MEDLINE
DCOM- 19990816
LR  - 20191023
IS  - 0022-1007 (Print)
IS  - 0022-1007 (Linking)
VI  - 190
IP  - 2
DP  - 1999 Jul 19
TI  - ITM2A is induced during thymocyte selection and T cell activation and causes
      downregulation of CD8 when overexpressed in CD4(+)CD8(+) double positive
      thymocytes.
PG  - 217-28
AB  - To identify novel genes that are involved in positive selection of thymocytes, we
      performed polymerase chain reaction (PCR)-based subtractive hybridization between
      selecting and nonselecting thymi. OT-1 T cell receptor (TCR) transgenic
      thymocytes on a recombination activating gene (RAG) null background are
      efficiently selected into the CD8 lineage in H-2(b) mice (RAG-2(-/-)OT-1,
      selecting thymi), but are not selected on a transporter associated with antigen
      processing (TAP) null background (RAG-2(-/-)TAP-1(-/-)OT-1, nonselecting thymi). 
      We report here our studies of one gene, ITM2A, whose expression is dramatically
      higher in T cells in the selecting thymus. The expression pattern of ITM2A in
      thymocyte subsets correlates with upregulation during positive selection. In
      addition, ITM2A expression is higher in the thymus than in either the spleen or
      lymph nodes, but can be upregulated in peripheral T cells upon activation. ITM2A 
      expression was also induced in RAG-2(-/-) thymocytes in vivo upon CD3
      cross-linking. We demonstrate that ITM2A is a type II membrane glycoprotein that 
      exists as two species with apparent M(r) of 45 and 43 kD and appears to localize 
      primarily to large cytoplasmic vesicles and the Golgi apparatus, but is also
      expressed on the cell surface. Expression on the surface of EL4 cells increases
      with activation by phorbol myristate acetate (PMA) and ionomycin. Finally,
      overexpression of ITM2A under control of the lck proximal promoter in mice
      results in partial downregulation of CD8 in CD4(+)CD8(+) double positive (DP)
      thymocytes, and a corresponding increase in the number of CD4(+)CD8(lo)
      thymocytes. Possible roles for this novel activation marker in thymocyte
      development are discussed.
FAU - Kirchner, J
AU  - Kirchner J
AD  - Howard Hughes Medical Institute and the Department of Immunology, University of
      Washington, Seattle, Washington 98195, USA.
FAU - Bevan, M J
AU  - Bevan MJ
LA  - eng
GR  - Howard Hughes Medical Institute/United States
GR  - AI29802/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Exp Med
JT  - The Journal of experimental medicine
JID - 2985109R
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 2)
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (CD4 Antigens)
RN  - 0 (CD8 Antigens)
RN  - 0 (DNA Primers)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (ITM2A protein, human)
RN  - 0 (Itm2a protein, mouse)
RN  - 0 (Membrane Proteins)
RN  - 0 (Rag2 protein, mouse)
RN  - 0 (TAP1 protein, human)
RN  - 0 (Tap1 protein, mouse)
RN  - 0 (V(D)J recombination activating protein 2)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily B, Member 2
MH  - ATP-Binding Cassette Transporters/genetics
MH  - Animals
MH  - Base Sequence
MH  - CD4 Antigens/*metabolism
MH  - CD8 Antigens/*metabolism
MH  - Cell Differentiation
MH  - DNA Primers/genetics
MH  - DNA-Binding Proteins/genetics
MH  - Down-Regulation
MH  - Female
MH  - Lymphocyte Activation
MH  - Male
MH  - Membrane Proteins/*biosynthesis/chemistry/*genetics
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - T-Lymphocyte Subsets/cytology/*immunology/*metabolism
PMC - PMC2195576
EDAT- 1999/08/04 00:00
MHDA- 1999/08/04 00:01
CRDT- 1999/08/04 00:00
PHST- 1999/08/04 00:00 [pubmed]
PHST- 1999/08/04 00:01 [medline]
PHST- 1999/08/04 00:00 [entrez]
AID - 10.1084/jem.190.2.217 [doi]
PST - ppublish
SO  - J Exp Med. 1999 Jul 19;190(2):217-28. doi: 10.1084/jem.190.2.217.