Bour H, Horvath C, Lurquin C, Cerottini J C, MacDonald H R
Ludwig Institute for Cancer Research, University of Lausanne, Epalinges, Switzerland.
J Immunol. 1998 Jun 1;160(11):5522-9.
Previous studies in our laboratory have shown that DBA/2 mice injected i.p. with syngeneic P815 tumor cells transfected with the HLA-CW3 gene (P815-CW3) showed a dramatic expansion of activated CD8+CD62L- T cells expressing exclusively the Vbeta10 segment. We have used this model to study the regulatory mechanisms involved in the development of the CW3-specific CD8+ response, with respect to different routes of immunization. Whereas both intradermal (i.d.) and i.p. immunization of DBA/2 mice with P815-CW3 cells led to a strong expansion of CD8+CD62L-Vbeta10+ cells, only the i.d. route allowed this expansion after immunization with P815 cells transfected with a minigene coding for the antigenic epitope CW3 170-179 (P815 miniCW3). Furthermore, depletion of CD4+ T cells in vivo completely abolished the specific response of CD8+CD62L-Vbeta10+ cells and prevented the rejection of P815-CW3 tumor cells injected i.p., whereas it did not affect CD8S+CD62L-Vbeta10+ cell expansion after i.d. immunization with either P815-CW3 or P815 miniCW3. Finally, the CW3-specific CD8+ memory response was identical whether or not CD4+ T cells were depleted during the primary response. Collectively, these results suggest that the CD8+ T cell response to P815-CW3 tumor cells injected i.p. is strictly dependent upon recognition of a helper epitope by CD4+ T cells, whereas no such requirement is observed for i.d. injection.
我们实验室之前的研究表明，腹腔注射转染了HLA - CW3基因的同基因P815肿瘤细胞（P815 - CW3）的DBA/2小鼠，其表达唯一Vbeta10片段的活化CD8⁺CD62L⁻ T细胞显著扩增。我们利用该模型研究了关于不同免疫途径的CW3特异性CD8⁺应答发育过程中涉及的调节机制。虽然用P815 - CW3细胞对DBA/2小鼠进行皮内（i.d.）和腹腔免疫均导致CD8⁺CD62L⁻Vbeta10⁺细胞强烈扩增，但仅皮内途径在用编码抗原表位CW3 170 - 179的小基因转染的P815细胞（P815 miniCW3）免疫后允许这种扩增。此外，体内CD4⁺ T细胞的耗竭完全消除了CD8⁺CD62L⁻Vbeta10⁺细胞的特异性应答，并阻止了腹腔注射的P815 - CW3肿瘤细胞的排斥，而在用P815 - CW3或P815 miniCW3进行皮内免疫后，它并不影响CD8⁺CD62L⁻Vbeta10⁺细胞的扩增。最后，无论在初次应答期间CD4⁺ T细胞是否被耗竭，CW3特异性CD8⁺记忆应答都是相同的。总体而言，这些结果表明，对腹腔注射的P815 - CW3肿瘤细胞的CD8⁺ T细胞应答严格依赖于CD4⁺ T细胞对辅助表位的识别，而皮内注射则未观察到这种需求。
