Peripheral blood progenitor cell product contains Th1-biased noninvariant CD1d-reactive natural killer T cells: implications for posttransplant survival.
OBJECTIVE
Bone marrow (BM) Th1 populations can contribute to graft-vs-leukemia responses. Granulocyte/granulocyte macrophage colony-stimulating factor (CSF)-mobilized peripheral blood progenitor cells (PBPC) have become widely accepted alternatives to BM transplantation. T cells coexpressing natural killer cell proteins (NKT) include a CD1d-reactive subset that influences immunity by rapidly producing large amounts of Th1 and/or Th2 cytokines dependent upon microenvironment and disease. There are two types of CD1d-reactive NKT. iNKT express a semi-invariant T-cell receptor-alpha. Other noninvariant CD1d-reactive NKT from BM and liver produce large amounts of interleukin-4 or interferon-gamma, respectively, and within the intestine can be biased in either direction. Recent data suggests that NKT might contribute to clinical benefits of PBPC.


METHODS
To address these issues, we phenotypically and functionally studied PBPC NKT.


RESULTS
Similarly to BM, NKT-like cells were common in allogeneic and autologous PBPC, there were relatively few classical iNKT, but high CD1d-reactivity concentrated in NKT fractions. Significantly, PBPC CD1d-reactive cells were relatively Th1-biased and their presence was associated with better prognosis. Granulocyte CSF treatment of BM to yield PBPC in vivo as well as in vitro Th2-polarizes conventional T cells and iNKT. However, granulocyte CSF treatment of BM in vitro produced Th1-biased NKT, providing a mechanism for opposite polarization of NKT from BM vs PBPC.


CONCLUSIONS
These results suggest distinct Th1 CD1d-reactive NKT cells could stimulate anti-tumor responses from those previously described, which can suppress graft-vs-host disease.
Shaulov
Angela
A
Department of Hematology-Oncology Beth Israel-Deaconess Medical Center, Boston, Mass. 02215, USA.
Yue
Simon
S
Wang
Ruojie
R
Joyce
Robin M
RM
Balk
Steven P
SP
Kim
Haesook T
HT
Avigan
David E
DE
Uhl
Lynne
L
Sackstein
Robert
R
Exley
Mark A
MA
D000328:Adult; D018949:Antigens, CD1 / Q000276:immunology*; D055610:Antigens, CD1d; D002469:Cell Separation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D006689:Hodgkin Disease / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000276:immunology*; D033581:Stem Cell Transplantation; D015996:Survival Rate; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology*; D016896:Treatment Outcome
D018949:Antigens, CD1; D055610:Antigens, CD1d; C526877:CD1D protein, human; D016178:Granulocyte-Macrophage Colony-Stimulating Factor