CD4 T cell memory is fundamental for long-lasting immunity and effective secondary responses following infection or vaccination. We have previously found that memory CD4 T cells specific for systemic antigens preferentially reside in the bone marrow (BM) and arise from splenic CD49b⁺T-bet⁺ CD4 T cells. However, how BM-homing memory precursors are generated during an immune reaction is unknown. We show here that BM memory precursors are generated via augmented rates of cell division throughout a primary immune response. Treatment with the cytostatic drug cyclophosphamide or blockade of the CD28/B7 co-stimulatory pathway at the beginning of the contraction phase abrogates the generation of BM memory precursors. We determine that, following a critical number of cell divisions, memory precursors downregulate CCR7 and upregulate IL-2Rβ, indicating that loss of CCR7 and gain of IL-2 signal are required for the migration of memory precursors toward the BM.

CD4 T细胞记忆对于感染或接种疫苗后的持久免疫力和有效的次级反应至关重要。我们之前已经发现，特异性针对全身性抗原的记忆CD4 T细胞优先驻留在骨髓（BM）中，并由脾CD49b ⁺ T-bet ⁺CD4 T细胞。然而，尚不清楚在免疫反应期间如何产生BM归巢记忆前体。我们在这里显示，BM记忆前体是通过整个主要免疫反应中细胞分裂的速率增加而产生的。在收缩期开始时用抑制细胞生长的药物环磷酰胺治疗或阻断CD28 / B7共刺激途径可消除BM记忆前体的产生。我们确定，在关键数目的细胞分裂之后，记忆前体下调CCR7并上调IL-2Rβ，这表明记忆前体向BM迁移需要CCR7的损失和IL-2信号的获得。