Progressive differentiation and commitment of CD8+ T cells to a poorly cytolytic CD8low phenotype in the presence of IL-4
Progressive differentiation and commitment of CD8+ T cells to a poorly cytolytic CD8low phenotype in the presence of IL-4
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DOI：
10.4049/jimmunol.174.4.2021
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发表时间：
2005-02-15
影响因子：
4.4
通讯作者：
Kelso, A
中科院分区：
文献类型：
--
作者：
Kienzle, N;Olver, S;Kelso, A
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Exposure to IL-4 during activation of naive murine CD8(+) T cells leads to generation of IL-4-producing effector cells with reduced surface CD8, low perforin, granzyme B and granzyme C mRNA, and poor cytolytic function. We show in this study that maximal development of these cells depended on exposure to IL-4 for the first 5 days of activation. Although IL-4 was not required at later times, CD8 T cell clones continued to lose surface CD8 expression with prolonged culture, suggesting commitment to the CD8(low) phenotype. This state was reversible in early differentiation. When single CD8(low) cells from 4-day cultures were cultured without IL-4, 65% gave rise to clones that partly or wholly comprised CD8(high) cells; the proportion of reverted clones was reduced or increased when the cells were cloned in the presence of IL-4 or anti-IL-4 Ab, respectively. CD8 expression positively correlated with perforin and granzyme A, B, and C mRNA, and negatively correlated with IL-4 mRNA levels among these clones. By contrast, most CD8(low) cells isolated at later time points maintained their phenotype, produced IL-4, and exhibited poor cytolytic function after many weeks in the absence of exogenous IL-4. We conclude that IL-4-dependent down-regulation of CD8 is associated with progressive differentiation and commitment to yield IL-4-producing cells with little cytolytic activity. These data suggest that the CD4(-)CD8(-) cells identified in some disease states may be the product of a previously unrecognized pathway of effector differentiation from conventional CD8(+) T cells.