PMID- 10357884
OWN - NLM
STAT- MEDLINE
DCOM- 19990715
LR  - 20181013
IS  - 0008-8749 (Print)
IS  - 0008-8749 (Linking)
VI  - 194
IP  - 1
DP  - 1999 May 25
TI  - A diabetogenic gene prevents T cells from receiving costimulatory signals.
PG  - 90-7
AB  - T cell fate following antigen encounter is determined by several intracellular
      signals generated by the interaction of the T cell with an antigen-presenting
      cell. In the periphery activation requires T cell receptor signaling (signal one)
      in combination with costimulatory signals (signal two), usually provided through 
      the cognate interaction of CD28 and B7 molecules. Provision of signal one alone
      to purified murine peripheral T cells in vitro induces apoptosis or anergy rather
      than promoting activation. These T cells can be rescued from apoptosis if they
      are provided with costimulation supplied, for example, by engaging the CD28
      co-receptor with an anti-CD28 monoclonal antibody or by adding an exogenous
      source of interleukin-2. However, a majority of peripheral T cells from
      autoimmune, diabetes-prone Biobreeding (BB) rats exhibited different responses to
      these stimuli. T cells from these rats could not be rescued from apoptosis by
      costimulation. This was not due to the inability of BB-DP T cells to upregulate
      CD28 and the IL-2 receptor in response to TCR crosslinking. The failure of these 
      costimulatory interactions to rescue BB-DP T cells segregated with the
      diabetes-susceptibility gene iddm1. Iddm1 in the rat causes peripheral T cell
      lymphopenia, which is associated with a dramatically shortened peripheral T cell 
      life span. Our results indicate that a diabetogenic gene may contribute to
      autoimmunity by negating costimulatory signals important for the survival of
      long-lived peripheral T cells.
CI  - Copyright 1999 Academic Press.
FAU - Moore, J K
AU  - Moore JK
AD  - Department of Immunology, Department of Medicine, University of Colorado Health
      Sciences Center, 4200 E. Ninth Avenue, Denver, Colorado, 80262, USA.
FAU - Gold, D P
AU  - Gold DP
FAU - Dreskin, S C
AU  - Dreskin SC
FAU - Lernmark, A
AU  - Lernmark A
FAU - Bellgrau, D
AU  - Bellgrau D
LA  - eng
GR  - R01 DK026190/DK/NIDDK NIH HHS/United States
GR  - DK48805/DK/NIDDK 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  - Netherlands
TA  - Cell Immunol
JT  - Cellular immunology
JID - 1246405
RN  - 0 (CD28 Antigens)
RN  - 0 (Mitogens)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (Receptors, Interleukin-2)
RN  - 0 (Thy-1 Antigens)
RN  - 11028-71-0 (Concanavalin A)
SB  - IM
MH  - Animals
MH  - CD28 Antigens/immunology
MH  - Concanavalin A/pharmacology
MH  - Diabetes Mellitus, Type 1/*genetics/*immunology
MH  - Immunophenotyping
MH  - Mitogens/pharmacology
MH  - Rats
MH  - Rats, Inbred F344
MH  - Receptors, Antigen, T-Cell/immunology
MH  - Receptors, Interleukin-2/immunology
MH  - *Signal Transduction/genetics
MH  - T-Lymphocytes/*immunology
MH  - Thy-1 Antigens/immunology
EDAT- 1999/06/08 00:00
MHDA- 1999/06/08 00:01
CRDT- 1999/06/08 00:00
PHST- 1999/06/08 00:00 [pubmed]
PHST- 1999/06/08 00:01 [medline]
PHST- 1999/06/08 00:00 [entrez]
AID - 10.1006/cimm.1999.1501 [doi]
AID - S0008-8749(99)91501-0 [pii]
PST - ppublish
SO  - Cell Immunol. 1999 May 25;194(1):90-7. doi: 10.1006/cimm.1999.1501.