ANTIGEN-PRESENTING B-CELLS AND HELPER T-CELLS COOPERATIVELY MEDIATE INTRAVIRIONIC ANTIGENIC-COMPETITION BETWEEN INFLUENZA-A VIRUS SURFACE GLYCOPROTEINS
ANTIGEN-PRESENTING B-CELLS AND HELPER T-CELLS COOPERATIVELY MEDIATE INTRAVIRIONIC ANTIGENIC-COMPETITION BETWEEN INFLUENZA-A VIRUS SURFACE GLYCOPROTEINS
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DOI：
10.1073/pnas.84.19.6869
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发表时间：
1987-10-01
影响因子：
11.1
通讯作者：
KILBOURNE, ED
中科院分区：
文献类型：
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作者：
JOHANSSON, BE;MORAN, TM;KILBOURNE, ED
通过感染甲型流感病毒的H3 N2变异体引发的BALB/c小鼠的胃肠外疫苗接种导致响应于同源（H3 N2）疫苗的N2抗体的产生与响应于在N2免疫原性方面相等的H7 N2疫苗相比减少。我们现在研究了纯化的脾B和T淋巴细胞的相互作用，以确定血凝素（HA）影响的抗体反应神经氨酸酶（NA）的细胞基础。体外H3 N1（HA特异性）和H6 N2（NA特异性）重组体（重组）病毒刺激的B/T细胞混合物中T细胞增殖反应的测定使我们能够区分对HA和NA抗原的细胞反应。在分析B/T细胞混合物中使用析因设计，我们已经表明：（i）在B细胞和T细胞引发中，病毒内HA比NA占优势;（ii）在给予H3 N2疫苗加强剂的小鼠中出现H3特异性B细胞的增加，而在给予H7 N2疫苗加强剂的小鼠中出现N2特异性B细胞的增加;和（iii）记忆B细胞作为抗原呈递细胞发挥功能，并在有利于HA的病毒内HA-NA抗原竞争的介导中与记忆辅助T细胞相互作用。对NA抗原的应答的衰减有利于HA再感染，这阻止了对两种抗原的平衡免疫应答。目前的研究进一步明确了流感病毒感染的复杂免疫学。
Parenteral vaccination of BALB/c mice primed by infection with H3N2 variants of influenza A virus results in a reduced production of N2 antibody in response to homologous (H3N2) vaccine compared with the response to an H7N2 vaccine equal in N2 immunogenicity. We now have studied the interaction in vitro of purified splenic B and T lymphocytes from variably immunized mice to ascertain the cellular basis of the hemagglutinin (HA)-influenced antibody response to neuraminidase (NA). Assay of the proliferative response of T cells in B/T-cell mixtures stimulated by H3N1 (HA-specfic) and H6N2 (NA-specfic) reassortant (recombinant) viruses in vitro has enabled us to differentiate cellular responses to HA and NA antigens. Using a factorial design in analysis of B/T-cell mixtures, we have shown that: (i)intravirionic HA is dominant over NA in both B- and T-cell priming; (ii) an increase in H3-specific B cells occurs in mice administered boosters of H3N2 vaccine, and an increase in N2-specific B cells occurs in those given a booster of H7N2 vaccine; and (iii) memory B cells function as antigen-presenting cells and interact with memory helper T cells in the mediation of intravirionic HA-NA antigenic competition in favor of HA. The damping of response to the NA antigen in favor of HA with reinfection prohibits balanced immunologic response to the two antigens. The present studies define further the complex immunology of influenza virus infection.