Rôle de CD271 dans l'immunomodulation des cellules T
T lymphocytes play a pivotal role in the development of the immune response specific to a given antigen. They play an important role in the recognition and elimination of abnormal cells such as cancer cells or those infected with a pathogen. However, dysregulation of T cell function can lead to the development of autoimmune diseases. Thus, it is crucial to modulate the duration and the amplitude of the immune response. To this end, T cell function is tightly regulated by a network of costimulatory and coinhibitory molecules. These cosignaling molecules are essential modulators of the immune system and belong to the immunoglobulin and tumor necrosis factor receptor superfamilies (IgSF and TNFRSF). Despite intensive study of these protein families, the function for many IgSF and TNFRSF members remain largely unknown. CD271, the low affinity nerve growth factor receptor (NGF) (also known as NGFR, p75 neurotrophin receptor, and TNFRSF16) is particularly intriguing. In addition to its expression on neural crest-derived cells, CD271 is also expressed on diverse cancer cells and hematopoietic cells such as dendritic cells, as well as immunomodulatory cell types including mesenchymal stromal cells and myeloid-derived suppressor cells, suggesting that CD271 may be involved in the regulation of immune responses. Yet, little is known about its immunomodulatory properties. It has recently been shown that CD271 expression on melanoma cells can indirectly modulate T cell function through NGF-dependent downregulation of tumor antigens, thus allowing cancer immune evasion. Beyond the canonical neurotrophins, it has been suggested that CD271 binds to human CD80, a major costimulatory molecule mainly expressed on antigen presenting cells but that is also up-regulated on T cells after activation where it performs immunomodulatory functions. However, direct modulation of the immune response by CD271 has not yet been considered. Given that several members of the TNFRSF directly interact with T cells to modulate their function, we hypothesized that CD271 can directly modulate T cell function. Using in vitro T cell activation systems, we show that recombinant CD271-Fc protein inhibits T cell activation, proliferation, and production of pro-inflammatory cytokines. However, our studies suggest that the interaction of CD271 and CD80 is human specific, and CD271 also inhibits murine T cell activation, suggesting that CD271 acts independently of CD80 binding to modulate T cell function. Our studies identify CD271 as a potential cosignaling molecule implicated in the regulation of T cell function. Thus, further characterization of CD271 could lead to the development of anti-cancer therapies.
CD271 CD80 Immunomodulation Cancer T cell Cosignaling Immunotherapy Tumor necrosis factor receptor superfamily Immunoglobulin superfamily