Abstracts (complete list) - Wissenschaft Online

Kristina Allers, Désirée Kunkel, Verena Moos, Martin Eisenblätter, Christiane Stahl-
Hennig, Annette Schrod, Ralf Ignatius, Franz-Josef Kaup, Thomas Schneider
Migration patterns of activated versus non-activated nonhuman
primate T lymphocytes: preferential homing of
activated autologous CD8+ T cells in the rectal mucosa
Background: Adoptive cell transfer (ACT) is a promising approach to induce antitumour
immune responses in cancer patients. However, crucial for successful therapy is the
access of the transferred cells to the tumours. Little is known about the migration
patterns of in vitro activated primate T cells and their persistence in different anatomical
compartments after ACT. Here, we describe a model, which enables the long-term
tracking of T cells in the peripheral blood, secondary lymphoid tissues, or
gastrointestinal mucosa after re-infusion of autologous peripheral lymphocytes into
rhesus macaques.
Methods: PBMC from 4 or 3 rhesus macaques were activated with aCD3/aCD28 or not,
stained with CFSE and autologously re-injected. Blood samples, lymph node (LN) as
well as mucosal biopsies (duodenum, rectum) were collected at various time points over
28 days and analysed for the presence of labeled CD4+ and CD4- T cells using flow
cytometry.
Results: On d1 post transfer of activated cells the frequency of labeled cells was 0.2,
3.8 and 4.6% of total CD4+ T cells in blood, duodenum and rectum, respectively.
Within the CD4- T cells the frequency of labeled cells was 0.2% in blood and 6.7% in
the duodenum but as high as 27.5% in the rectal mucosa. 7 days post transfer of
activated cells 0.3, 0.6, 0.5 and 0.4% labeled CD4+ T cells were present in the blood,
LN, duodenum and rectum, respectively. Within the CD4- T cells the frequency of
labeled cells was 0.03% in the blood, 0.3% in LN and 2.9% in the duodenum. In the
rectal mucosa labeled cells constituted 29.6% of the total CD4- T cells indicating
persistence of activated CD8+ T cells in the rectal mucosa.
Conclusions: Injection of CFSE-labeled, autologous T cells into rhesus macaques allows
the tracking of lymphocyte migration to various anatomical compartments and thus
representing a pre-clinical model for the evaluation of T cell-based immunotherapy. Nonspecificly
activated CD8+ T cells preferentially migrate to and persist in the rectal
mucosa whereas activated CD4+ T cells are found in much less numbers at this site but
also in other compartments.