Gans Hayley A, Yasukawa Linda L, Zhang Cathryn Z, Wakim Rima Hanna, Rinki Mary, Dehovitz Ross, Arvin Ann M
Department of Pediatrics, Stanford University School of Medicine, Stanford, California 94305-5208, USA.
Viral Immunol. 2008 Jun;21(2):163-72. doi: 10.1089/vim.2007.0113.
Understanding the infant host response to measles vaccination is important because of their increased mortality from measles and the need to provide effective protection during the first year of life. Measles-specific T and B-cell responses are lower in infants after measles vaccination than in adults. To define potential mechanisms, we investigated age-related differences in measles-specific T-cell proliferation, CD40-L expression, and IFN-gamma production after measles immunization, and the effects of rhIL-12 and rhIL-15 on these responses. Measles-specific T-cell proliferation and mean IFN-gamma release from infant PBMCs were significantly lower when compared with responses of vaccinated children and adults. Infant responses increased to ranges observed in children and adults when both rhIL-12 and rhIL-15 were added to PBMC cultures. Furthermore, a significant rise in T-cell proliferation and IFN-gamma release was observed when infant PBMCs were stimulated with measles antigen in the presence of rhIL-12 and rhIL-15 compared to measles antigen alone. CD40-L expression by infant and adult T cells stimulated with measles antigen was comparable, but fewer infant CD40-L(+) T cells expressed IFN-gamma. These observations suggest that lower measles-specific T-cell immune responses elicited by measles vaccine in infants may be due to diminished levels of key cytokines.
了解婴儿对麻疹疫苗的宿主反应很重要,因为他们因麻疹导致的死亡率增加,且需要在生命的第一年提供有效的保护。麻疹疫苗接种后,婴儿体内麻疹特异性T细胞和B细胞反应低于成人。为了确定潜在机制,我们研究了麻疹免疫后麻疹特异性T细胞增殖、CD40-L表达和IFN-γ产生的年龄相关差异,以及重组人白细胞介素-12(rhIL-12)和重组人白细胞介素-15(rhIL-15)对这些反应的影响。与接种疫苗的儿童和成人的反应相比,婴儿外周血单个核细胞(PBMCs)的麻疹特异性T细胞增殖和平均IFN-γ释放显著降低。当将rhIL-12和rhIL-15都添加到PBMC培养物中时,婴儿的反应增加到儿童和成人中观察到的范围。此外,与单独用麻疹抗原刺激相比,当在rhIL-12和rhIL-15存在的情况下用麻疹抗原刺激婴儿PBMCs时,观察到T细胞增殖和IFN-γ释放显著增加。麻疹抗原刺激的婴儿和成人T细胞的CD40-L表达相当,但表达IFN-γ的婴儿CD40-L(+) T细胞较少。这些观察结果表明,麻疹疫苗在婴儿中引发的较低的麻疹特异性T细胞免疫反应可能是由于关键细胞因子水平降低所致。