Parretta Elisabetta, Cassese Giuliana, Barba Pasquale, Santoni Angela, Guardiola John, Di Rosa Francesca
Institute of Genetics and Biophysics, Adriano Buzzati Traverso, Consiglio Nazionale delle Ricerche, Naples, Italy.
J Immunol. 2005 Jun 15;174(12):7654-64. doi: 10.4049/jimmunol.174.12.7654.
Long-term persistence of Ag-experienced CD8 cells, a class of T lymphocytes with cytotoxic function, contributes to immunological memory against intracellular pathogens. After Ag clearance, memory CD8 cells are maintained over time by a slow proliferation, primarily cytokine driven. In this article, we show that the bone marrow (BM) is the crucial organ where such basal division of memory CD8 cells occurs. BM memory CD8 cells contain a higher percentage of proliferating cells than their corresponding cells in either spleen or lymph nodes from C57BL/6 mice. This occurs both in the case of memory-phenotype CD44(high) CD8 cells and in the case of Ag-specific memory CD8 cells. Importantly, the absolute number of Ag-specific memory CD8 cells dividing in the BM largely exceeds that in spleen, lymph nodes, liver, and lung taken together. In the BM, Ag-specific memory CD8 cells express lower levels of CD127, i.e., the alpha-chain of IL-7R, than in either spleen or lymph nodes. We interpret these results as indirect evidence that Ag-specific memory CD8 cells receive proliferative signals by IL-7 and/or IL-15 in the BM and propose that the BM acts as a saturable "niche" for the Ag-independent proliferation of memory CD8 cells. Taken together, our novel findings indicate that the BM plays a relevant role in the maintenance of cytotoxic T cell memory, in addition to its previously described involvement in long-term Ab responses.
具有细胞毒性功能的一类T淋巴细胞——抗原特异性CD8细胞的长期持续存在有助于对细胞内病原体产生免疫记忆。在抗原清除后，记忆性CD8细胞通过缓慢增殖得以长期维持，主要由细胞因子驱动。在本文中，我们表明骨髓是记忆性CD8细胞发生这种基础分裂的关键器官。与C57BL/6小鼠脾脏或淋巴结中的相应细胞相比，骨髓记忆性CD8细胞中增殖细胞的百分比更高。这在记忆表型CD44(高)CD8细胞以及抗原特异性记忆性CD8细胞的情况下均会发生。重要的是，在骨髓中进行分裂的抗原特异性记忆性CD8细胞的绝对数量大大超过脾脏、淋巴结、肝脏和肺中此类细胞数量的总和。在骨髓中，抗原特异性记忆性CD8细胞表达的CD127（即IL-7R的α链）水平低于脾脏或淋巴结中的细胞。我们将这些结果解释为间接证据，表明抗原特异性记忆性CD8细胞在骨髓中通过IL-7和/或IL-15接收增殖信号，并提出骨髓作为记忆性CD8细胞非抗原依赖性增殖的一个可饱和的“生态位”发挥作用。综上所述，我们的新发现表明，骨髓除了在先前描述的长期抗体反应中发挥作用外，在细胞毒性T细胞记忆的维持中也发挥着重要作用。
