Migration Patterns of Nonspecifically Activated Versus... : Journal of Immunotherapy (original) (raw)

Basic Studies

Migration Patterns of Nonspecifically Activated Versus Nonactivated Nonhuman Primate T Lymphocytes: Preferential Homing of Activated Autologous CD8+ T Cells in the Rectal Mucosa

Allers, Kristina*; Kunkel, Désirée* †; Moos, Verena*; Eisenblätter, Martin‡; Stahl-Hennig, Christiane§; Kaup, Franz-Josef§; Ignatius, Ralf‡; Schneider, Thomas*

*Medical Clinic I, Gastroenterology, Infectious Diseases and Rheumatology

‡Department of Infection Immunology, Institute of Microbiology and Hygiene, Charité-Campus Benjamin Franklin, Berlin

§Department of Virology and Immunology, German Primate Centre, Goettingen, Germany

†Unité de Régulation des Infections Rétrovirales, Institut Pasteur, Paris, France

Grant support: This project was supported by the German Research Foundation (DFG KFO grant 104/1-1).

Financial Disclosure: The authors have declared there are no financial conflicts of interest related to this work.

Reprints: Kristina Allers, Medical Clinic I Gastroenterology, Infectious Diseases and Rheumatology, Charité-Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany (e-mail: [email protected]).

Received for publication August 31, 2007; accepted November 19, 2007

Kristina Allers and Désirée Kunkel contributed equally to the study.

Abstract

Adoptive cell transfer may be a successful strategy in anticancer therapy and its therapeutic efficiency depends on the access of transferred cells to the tumor site and their persistence in vivo. Nevertheless, the migration properties of autologous in vitro-activated T cells in primates are largely unknown. Here, we established the long-term tracking of T-cell migration into various compartments of rhesus macaques as a preclinical model for the evaluation of T-cell–based immunotherapy. Peripheral blood mononuclear cells from 3 to 4 rhesus macaques were activated with anti-CD3/anti-CD28 or not, labeled with carboxyfluorescein diacetat succinimidyl ester, and reinjected intravenously into the donor animals. Blood samples, lymph node biopsies, and mucosal biopsies (duodenum, rectum) were collected at various time points and analyzed by flow cytometry for the presence of the reinjected T cells. We demonstrate that nonspecific in vitro activation changes the in vivo migratory behavior of T cells and provokes a preferential migration of CD8+ T cells to the rectum. Nonspecifically activated transferred CD4+ T cells were found in much lower frequencies at this site and also in other compartments. Thus, our results indicate an imbalanced distribution of autologous CD8+ and CD4+ T cells in various compartments that is more apparent when T cells are activated before the transfer. The migratory behavior of in vitro-expanded, autologously transferred T cells can, therefore, influence the clinical outcome of adoptive cell transfer.