Adkins Becky, Bu Yurong, Vincek Vladimir, Guevara Patricia
Department of Microbiology and Immunology, University of Miami Medical School, Miami, FL 33136, USA.
Clin Dev Immunol. 2003 Mar;10(1):43-51. doi: 10.1080/10446670310001598474.
Exposure of neonatal mice to antigen often results in Th2-biased responses in later life. Examples of this Th2 tendency are (a) secondary antibody responses dominated by the Th2-associated IgG1 isotype and (b) Th2-mediated tolerance to alloantigens. We previously reported that neonates develop primary Th1 and Th2 function in the lymph nodes but exclusive Th2 primary splenic responses. Here, we have tested whether the Th2 bias of adults initially immunized as neonates is due to the early, primary Th2 polarization in the spleen. Surprisingly, removal of the spleen at birth had no affect on either IgG1-dominant secondary responses or the development of tolerance to alloantigens. Thus, neonatal lymph nodes are sufficient to generate Th2-biased function following neonatal antigen exposure. To understand how this could arise, we examined the primary Th1/Th2 responses of CD4+ lymph node cells. Unlike the balanced Th1/Th2 responses seen with total lymph node cells, the primary responses of isolated CD4+ cells were skewed to IL-4 producing function. These results suggest that the early development of Th2-dominant responses by lymph node CD4+ cells contributes substantially to the subsequent development of Th2-dominant memory in neonates.
新生小鼠接触抗原后，在其后期生活中往往会导致偏向Th2的反应。这种Th2倾向的例子包括：（a）以Th2相关的IgG1同种型为主导的二次抗体反应，以及（b）Th2介导的对同种异体抗原的耐受性。我们之前报道过，新生小鼠在淋巴结中会发展出初始的Th1和Th2功能，但在脾脏中则只有Th2主导的初始反应。在此，我们测试了最初在新生期免疫的成年小鼠中出现的Th2偏向是否归因于脾脏中早期的初始Th2极化。令人惊讶的是，出生时切除脾脏对IgG1主导的二次反应或对同种异体抗原耐受性的发展均无影响。因此，新生小鼠的淋巴结足以在新生期接触抗原后产生偏向Th2的功能。为了理解这是如何发生的，我们检测了CD4⁺淋巴结细胞的初始Th1/Th2反应。与总淋巴结细胞呈现的平衡Th1/Th2反应不同，分离出的CD4⁺细胞的初始反应偏向于产生IL-4的功能。这些结果表明，淋巴结CD4⁺细胞早期Th2主导反应的发展对新生小鼠随后Th2主导记忆的形成有很大贡献。
