PMID- 7964463
OWN - NLM
STAT- MEDLINE
DCOM- 19941201
LR  - 20190508
IS  - 0022-1007 (Print)
IS  - 1540-9538 (Electronic)
IS  - 0022-1007 (Linking)
VI  - 180
IP  - 5
DP  - 1994 Nov 1
TI  - Anti-SCID mouse reactivity shapes the human CD4+ T cell repertoire in hu-PBL-SCID 
      chimeras.
PG  - 1817-27
AB  - Injecting human peripheral blood mononuclear cells into severe combined 
      immunodeficient (SCID) mice results in long-term engraftment of human 
      lymphocytes, of which > 98% are phenotypically mature, activated T cells. Here we 
      have characterized the human T cells that populate such hu-PBL-SCID chimeras. We 
      report that these human T cells do not mobilize Ca2+ after CD3 stimulation, i.e., 
      their T cell receptor (TCR)-mediated signal transduction is deficient. 
      Chimera-derived human T cells do not secrete lymphokines or undergo blastogenesis 
      after CD3 stimulation, but proliferate in response to interleukin 2 (IL-2), 
      defining the chimera derived human T cells as anergic. Anergy was seen in both 
      the CD4+ and the CD8+ subpopulations. We established human T cell lines from 
      chimeras. These T cells retained their anergic state for 1-2 mo in culture, after 
      which they simultaneously regained the ability to mobilize Ca2+, secrete 
      lymphokines, and to undergo blastogenesis following stimulation via the TCR. Once 
      regaining proliferative responsiveness to CD3 stimulation, these CD4+ T cell 
      lines displayed anti-SCID mouse reactivity and showed no specificity for recall 
      antigens. All CD3-responsive CD4+ T cell clones obtained from such lines were 
      SCID mouse specific, recognizing native major histocompatibility complex class II 
      products on the murine cells. In contrast, chimera-derived human CD8+ cell lines 
      and clones did not display detectable anti-mouse reactivity. The data show that 
      the human T cell system in long term hu-PBL-SCID chimeras is nonfunctional due to 
      both anergy and the limitation of the CD4+ repertoire to xenoreactive clones. The 
      data suggest that long-term hu-PBL-SCID chimerism represents an atypical 
      graft-versus-host reaction in which the human effector T cells become anergic in 
      the murine environment.
FAU - Tary-Lehmann, M
AU  - Tary-Lehmann M
AD  - Hart and Louise Lyon Laboratory, Department of Medicine, University of California 
      at Los Angeles 90024.
FAU - Lehmann, P V
AU  - Lehmann PV
FAU - Schols, D
AU  - Schols D
FAU - Roncarolo, M G
AU  - Roncarolo MG
FAU - Saxon, A
AU  - Saxon A
LA  - eng
GR  - AI-28697/AI/NIAID NIH HHS/United States
GR  - CA-12800/CA/NCI 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 (CD3 Complex)
RN  - 0 (Cytokines)
RN  - 0 (Interleukin-2)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Adult
MH  - Animals
MH  - CD3 Complex/immunology
MH  - CD4-Positive T-Lymphocytes/*immunology
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Calcium/metabolism
MH  - Cell Line
MH  - Chimera/*immunology
MH  - Cytokines/biosynthesis
MH  - Female
MH  - Graft vs Host Reaction
MH  - Humans
MH  - Interleukin-2/pharmacology
MH  - Lymphocyte Activation
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, SCID/*immunology
MH  - Middle Aged
PMC - PMC2191753
EDAT- 1994/11/01 00:00
MHDA- 1994/11/01 00:01
PMCR- 1995/05/01
CRDT- 1994/11/01 00:00
PHST- 1994/11/01 00:00 [pubmed]
PHST- 1994/11/01 00:01 [medline]
PHST- 1994/11/01 00:00 [entrez]
PHST- 1995/05/01 00:00 [pmc-release]
AID - 95053712 [pii]
AID - 10.1084/jem.180.5.1817 [doi]
PST - ppublish
SO  - J Exp Med. 1994 Nov 1;180(5):1817-27. doi: 10.1084/jem.180.5.1817.