|
|
 Previous Article | Table of Contents | Next Article 
Blood, 1 June 2002, Vol. 99, No. 11, pp. 4053-4062
IMMUNOBIOLOGY
Defective T-helper cell function after T-cell-depleting
therapy affecting naive and memory populations
Andreas Heitger,
Patricia Winklehner,
Petra Obexer,
Johannes Eder,
Claudia Zelle-Rieser,
Gabriele Kropshofer,
Martin Thurnher, and
Wolfgang Holter
From the University Children's Hospital Innsbruck;
Department of Urology, University Innsbruck, Austria; Children's
Cancer Research Institute, St Anna Children's Hospital Vienna,
Austria.
Impaired T-cell function after T-cell- depleting (TCD) therapy
has been hypothesized to be related to a transient predominance of
extrathymically expanding memory T cells. To test whether after TCD
therapy the naive T-helper cell population is functionally intact, the
in vitro immune response of CD4+CD45RA+ (naive)
and of CD4+CD45RA (memory) cells to
polyclonal mitogens (immobilized anti-CD3, phytohemagglutinin) was
analyzed by flow cytometry in 22 pediatric patients after high-dose
chemotherapy (including 5 after autologous and 5 after allogeneic stem
cell support). At 1 to 3 months after TCD therapy, patient samples
showing decreased lymphoproliferative responses also showed a reduced
induction of the early activation marker CD69 by CD4+ T
cells from 4 to 72 hours after stimulation even when supplemented with
exogenous interleukin-2. This defect affected
CD4+CD45RA cells, but, strikingly, also
CD4+CD45RA+ cells, including samples in which
CD4+CD45RA+ cells were more than 90/µL, thus
indicating ongoing thymopoiesis. Histogram analyses showed the median
peak channel of CD69 in control CD4+CD45RA+
cells rising 98-fold (median) but only 28-fold in patient cells (P < .0001). Apoptosis as detected by annexin V staining
was increased in resting patient CD4+ T cells (25% versus
6%) and also affected CD4+CD45RA+ cells (12%
versus 5%, P < .01). When peripheral blood mononuclear cells (PBMCs) were enriched for T cells, stimulatory responses of
CD4+ cells and of CD4+CD45RA+ cells
markedly improved. Thus, after TCD therapy suppressor factors contained
in the non-T-cell fraction of PBMCs may affect T-helper cells
irrespective of their naive or memory phenotype thus extending T-cell
dysfunction to the presumably thymus-dependently regenerated T cells.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
B. Jurgens, U. Hainz, D. Fuchs, T. Felzmann, and A. Heitger
Interferon-{gamma}-triggered indoleamine 2,3-dioxygenase competence in human monocyte-derived dendritic cells induces regulatory activity in allogeneic T cells
Blood,
October 8, 2009;
114(15):
3235 - 3243.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. D. K. D. Sewgobind, M. M. L. Kho, L. J. W. van der Laan, T. K. Hendrikx, T. van Dam, H. W. Tilanus, J. N. M. IJzermans, W. Weimar, and C. C. Baan
The effect of rabbit anti-thymocyte globulin induction therapy on regulatory T cells in kidney transplant patients
Nephrol. Dial. Transplant.,
May 1, 2009;
24(5):
1635 - 1644.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
U. Hainz, P. Obexer, C. Winkler, P. Sedlmayr, O. Takikawa, H. Greinix, A. Lawitschka, U. Putschger, D. Fuchs, S. Ladisch, et al.
Monocyte-mediated T-cell suppression and augmented monocyte tryptophan catabolism after human hematopoietic stem-cell transplantation
Blood,
May 15, 2005;
105(10):
4127 - 4134.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Damiani, R. Stocchi, P. Masolini, A. Michelutti, A. Geromin, A. Sperotto, C. Skert, M. Michieli, M. Baccarani, and R. Fanin
CD34+-selected versus unmanipulated autologous stem cell transplantation in multiple myeloma: impact on dendritic and immune recovery and on complications due to infection
Ann. Onc.,
March 1, 2003;
14(3):
475 - 480.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
