Department of Molecular Microbiology and Immunology, Malaria Research Institute, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America.
PLoS One. 2011 Jan 4;6(1):e15948. doi: 10.1371/journal.pone.0015948.
CD4(+) helper T cells are critical orchestrators of immune responses to infection and vaccination. During primary responses, naïve CD8(+) T cells may need "CD4 help" for optimal development of memory populations. The immunological factors attributed to CD4 help depend on the context of immunization and vary depending on the priming system. In response to immunization with radiation-attenuated Plasmodium yoelii sporozoites, CD8(+) T cells in BALB/c mice fail to generate large numbers of effector cells without help from CD4(+) T cells--a defect not observed in most systems. Given this unique early dependence on CD4 help, we evaluated the effects of CD4(+) cells on the development of functional properties of CD8(+) T cells and on their ability to abolish infection. First, we determined that this effect was not mediated by CD4(+) non-T cells and did not involve CD1d-restricted NKT cells. We found that CD8(+) T cells induced by sporozoites without CD4 help formed memory populations severely reduced in magnitude that could not limit parasite development in the liver. The inability of these "helpless" memory T cells to protect is not a result of defects in effector function, as their capacity to produce cytokines and undergo cytotoxic degranulation was indistinguishable from control memory T cells. These data indicate that CD4(+) T help may not be necessary to develop the functional attributes of CD8(+) T cells; however they are crucial to ensure the survival of effector and memory cells induced in primary responses.
CD4(+)辅助 T 细胞是感染和疫苗接种免疫反应的关键协调者。在初次反应中，幼稚 CD8(+)T 细胞可能需要“CD4 帮助”才能最佳地发育为记忆细胞群体。归因于 CD4 帮助的免疫因素取决于免疫接种的背景，并因启动系统而异。在用辐射减毒的 Plasmodium yoelii 孢子虫感染 BALB/c 小鼠后，CD8(+)T 细胞在没有 CD4(+)T 细胞帮助的情况下无法产生大量效应细胞——这在大多数系统中都没有观察到。鉴于这种对 CD4 帮助的独特早期依赖性，我们评估了 CD4(+)细胞对 CD8(+)T 细胞功能特性的发展以及对其消除感染能力的影响。首先，我们确定这种效应不是由 CD4(+)非 T 细胞介导的，也不涉及 CD1d 限制的 NKT 细胞。我们发现，没有 CD4 帮助诱导的孢子虫 CD8(+)T 细胞形成的记忆细胞群体数量严重减少，无法限制肝脏中的寄生虫发育。这些“无助”记忆 T 细胞无法保护的原因不是效应功能缺陷，因为它们产生细胞因子和经历细胞毒性脱颗粒的能力与对照记忆 T 细胞无法区分。这些数据表明，CD4(+)T 辅助可能不是发育 CD8(+)T 细胞功能属性所必需的；然而，它们对于确保在初次反应中诱导的效应细胞和记忆细胞的存活至关重要。
