CD8+ Memory T Lymphocytes from Bone Marrow— Immune Function and Therapeutic Potential

Abstract

Immunity to previously encountered diseases is provided in large part by memory T lymphocytes, which may be subdivided based on phenotypic and functional differences, as well as the specific cellular compartments in which these cells reside. The bone marrow (BM) is a unique microenvironment that supports robust proliferation and recall responses of both "central" and "effector" memory T cells, particularly within the CD8+ T cell subset. The recent identification within human BM of a population of CD8+ effector memory T cells with hybrid phenotype and enhanced cytotoxic function has important implications for the development of future immunotherapies. Using activated BM CD8+ memory T cells for adoptive transfer or targeting such cells with tailored vaccines may improve the ability of these classic modalities to produce potent and long-lasting antigen-specific responses, ultimately leading to clinically significant control of viral and malignant diseases.

Emergence of BCR-ABL–specific cytotoxic T cells in the bone marrow of patients with Ph+ acute lymphoblastic leukemia during long-term imatinib mesylate treatment

“…26 This observation suggests that in Ph ϩ ALL patients in complete remission the normal differentiation, recirculation, and activation potential of BM T lymphocytes do not appear to be negatively affected, even during high-dose IM. In patient 1, who showed sustained complete molecular remission, the almostexclusive presence of the EMRA subset among BM CD8 ϩ T cells may possibly be consistent with the notion that EMRA T cells appear late during the immune response and proliferate in the absence of the antigen.…”

Age related changes in T cell mediated immune response and effector memory to Respiratory Syncytial Virus (RSV) in healthy subjects

“…In this context, antigen specific CD8 + T cells which express interleukin-7 receptor α (CD127 + ) show enhanced proliferation in response to homeostatic signals and most likely develop into long-lasting memory cells. IL-7 stimulation is crucial for memory T cell survival and proliferation, and a high IL-7Rα/CD127 expression warrants these cells with the ability to persist for long period in the absence of antigen stimulation [21,36]. CD127 may therefore, be considered as a useful marker to identify effector lymphocytes precursors destined to differentiate into memory cells [22].…”

“…It is essential that the RSV specific memory T cells persist after primary infection to keep enduring immunological protection. The mechanisms behind the development of long-lasting memory cells are incompletely understood but, recently, it was shown that IL-7Rα + effector cells are able to survive antigen deprivation and develop into long living memory CD8 + T cells [22,36]. To this aim, we characterized the CD8 + CD127 + long-lasting memory cells specific to RSV by pentamer in healthy subjects of three different age groups.…”

Three-Dimensional Tumor Model and T-Lymphocytes Immunotherapy for Cancer

“…Some current cancer vaccine strategies may fail because they amplify, rather than correct or reset, the corrupted CD81 memory population. 26 However, it is becoming apparent that highly activated effector cells may become terminally differentiated, display impaired proliferation and survival in vivo, and mediate short-term antitumor effects.…”