Antigen distribution drives programmed antitumor CD8 cell migration and determines its efficiency.
Understanding both the role of tumor Ag in CD8 cell differentiation and the reasons that CD8 cells may work inefficiently is crucial for therapeutic approaches in cancer. We studied OT-1 CD8 cell responses in vivo in a differential Ag-distribution model that used EG-7, the EL-4 thymoma transfected with OVA. On their initial Ag encounter, OT-1 CD8 cells underwent programmed expansion in the lymph nodes, where they acquired the ability to migrate to the encapsulated tumor site after > or =4 divisions, without continuous antigenic stimulation. This short antigenic stimulation was sufficient to induce the migration differentiation program, which included modulation of chemokine receptor mRNA expression and down-regulation of CD62L. Moreover, Ag quantity determined the behavior of the OT-1 CD8 cells, including their effector functions and sensitivity to apoptosis. Thus, the initial Ag encounter drives the programmed cell migration potencies, but neither effector functions nor cell death can occur without continuous TCR triggering.
Boissonnas
Alexandre
A
Laboratoire d'Immunologie Cellulaire, Institut National de la Santé et de la Recherche Médicale, Unité 543, Faculté de Médecine Pitié-Salpêtrière, 91 Boulevard de l'Hôpital, 75634 Paris cedex 13, France.
Combadiere
Christophe
C
Lavergne
Elise
E
Maho
Maud
M
Blanc
Catherine
C
Debré
Patrice
P
Combadiere
Behazine
B
D000818:Animals; D000951:Antigens, Neoplasm / Q000032:analysis*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002465:Cell Movement; D003602:Cytotoxicity, Immunologic; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000628:therapy; D010047:Ovalbumin / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D019707:Receptors, Chemokine / Q000032:analysis
D000951:Antigens, Neoplasm; D011948:Receptors, Antigen, T-Cell; D019707:Receptors, Chemokine; D007371:Interferon-gamma; D010047:Ovalbumin