Pre-B acute lymphoblastic leukemia cells may induce T-cell anergy to alloantigen
| Autor: | Aa, Cardoso, Joachim Schultze, Va, Boussiotis, Gj, Freeman, Mj, Seamon, Laszlo S, Billet A, Se, Sallan, Jg, Gribben, Lm, Nadler |
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| Předmět: |
Clonal Anergy
Antigen Presentation Isoantigens Membrane Glycoproteins Interleukin-7 Immunology Antigen-Presenting Cells Receptors Interleukin-2 Cell Biology Hematology Flow Cytometry Lymphocyte Activation Biochemistry Immunophenotyping Antigens CD Antigens Neoplasm T-Lymphocyte Subsets Precursor B-Cell Lymphoblastic Leukemia-Lymphoma B7-1 Antigen Immune Tolerance Neoplastic Stem Cells Humans Interleukin-2 B7-2 Antigen Interleukin-4 |
| Zdroj: | Europe PubMed Central |
| Popis: | Even if neoplastic cells express tumor associated antigens they still may fail to function as antigen presenting cells (APC) if they lack expression of one or more molecules critical for the induction of productive immunity. These cellular defects can be repaired by physiologic activation, transfection, or fusion of tumor cells with professional APC. Although such defects can be repaired, antitumor specific T cells may still fail to respond in vivo if they may have been tolerized. Here, human pre-B cell acute lymphoblastic leukemia (pre-B ALL) was used as a model to determine if primary human tumor cells can function as alloantigen presenting cells (alloAPC) or alternatively whether they induce anergy. In the present report, we show that pre-B cell ALL express alloantigen and adhesion molecules but uniformly lack B7–1 (CD80) and only a subset express B7–2 (CD86). Pre-B ALL cells are inefficient or ineffective alloAPC and those cases that lack expression of B7–1 and B7–2 also induce alloantigen specific T- cell unresponsiveness. Under these circumstances, T-cell unresponsiveness could be prevented by physiologic activation of tumor cells via CD40, cross-linking CD28, or signaling through the common gamma chain of the interleukin-2 receptor on T cells. Taken together, these results suggest that pre-B ALL may be incapable of inducing clinically significant T-cell-mediated antileukemia responses. This defect may be not only due to their inability to function as APC, but also due to their potential to induce tolerance. Attempts to induce clinically significant antitumor immune responses may then require not only mechanisms to repair the antigen presenting capacity of the tumor cells, but also reversal of tolerance. |
| Databáze: | OpenAIRE |
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