PMID- 16766227
OWN - NLM
STAT- MEDLINE
DCOM- 20060907
LR  - 20181201
IS  - 1521-6616 (Print)
IS  - 1521-6616 (Linking)
VI  - 120
IP  - 2
DP  - 2006 Aug
TI  - Autoimmunity during lymphopenia: a two-hit model.
PG  - 121-8
AB  - The immune system has evolved elaborate mechanisms to respond to diverse antigens 
      while minimizing the risk for autoimmune reactivity. During lymphopenia, however, 
      some mechanisms that normally serve to maintain host tolerance are temporarily 
      suspended. Peripheral T cells proliferate in response to self-antigens in 
      lymphopenic hosts, but proliferation toward these same antigens is prevented when 
      T cell numbers are normal. This process, termed homeostatic peripheral expansion, 
      augments peripheral T cell number and limits repertoire skewing during recovery 
      from lymphopenia and also predisposes lymphopenic hosts to autoimmune disease. 
      This paper reviews murine and human settings in which autoimmunity occurs in the 
      context of lymphopenia. We propose a two-hit model, in which lymphopenia plus 
      another insult is sufficient to induce autoimmune disease. Among the secondary 
      insults that appear sufficient to induce autoimmunity during lymphopenia are 
      overproduction of IL-21 as occurs in the NOD.SCID mouse, depletion of Tregs as 
      demonstrated in murine colitis and gastritis models, and tissue inflammation as 
      seen in HIV infected patients who develop immune reconstitution inflammatory 
      syndrome (IRIS). Delineating critical cofactors which result in autoimmune 
      disease during lymphopenia can provide insight into the pathophysiology of 
      naturally occurring autoimmune diseases as well as generating testable hypothesis 
      for inducing tumor-specific autoimmunity in lymphopenic hosts with cancer.
FAU - Krupica, Tom Jr
AU  - Krupica T Jr
AD  - Pediatric Oncology Branch, National Cancer Institute, Bethesda, MD 20892, USA.
FAU - Fry, Terry J
AU  - Fry TJ
FAU - Mackall, Crystal L
AU  - Mackall CL
LA  - eng
GR  - Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - United States
TA  - Clin Immunol
JT  - Clinical immunology (Orlando, Fla.)
JID - 100883537
RN  - 0 (Interleukins)
RN  - MKM3CA6LT1 (interleukin-21)
SB  - IM
MH  - Animals
MH  - Autoimmune Diseases/*complications/*etiology/immunology
MH  - Disease Models, Animal
MH  - Homeostasis
MH  - Humans
MH  - Interleukins/biosynthesis
MH  - Lymphocyte Activation
MH  - Lymphopenia/*complications
MH  - Mice
MH  - *Models, Immunological
MH  - T-Lymphocytes/cytology/immunology/physiology
RF  - 61
EDAT- 2006/06/13 09:00
MHDA- 2006/09/08 09:00
CRDT- 2006/06/13 09:00
PHST- 2006/01/11 00:00 [received]
PHST- 2006/04/12 00:00 [revised]
PHST- 2006/04/14 00:00 [accepted]
PHST- 2006/06/13 09:00 [pubmed]
PHST- 2006/09/08 09:00 [medline]
PHST- 2006/06/13 09:00 [entrez]
AID - S1521-6616(06)00694-2 [pii]
AID - 10.1016/j.clim.2006.04.569 [doi]
PST - ppublish
SO  - Clin Immunol. 2006 Aug;120(2):121-8. doi: 10.1016/j.clim.2006.04.569.