The reasons why IL-4KO mice fail to mount a vigorous antibody production when injected with IL-4 in low doses, even if complexed with specific monoclonal antibodies which are themselves immunogenic, and helped by powerful adjuvants such as CFA/IFA and Alum, are interesting on their own right and potentially important for the exploration of this approach. I believe the experimental results described, which are essentially negative, reflect studies which are methodologically correct, although positive controls using higher doses of IL-4 were not shown. My major reservations refer to: a) the manuscript itself, which is very difficult to follow, both from an imperfect use of English at numerous passages, and from the lack of attention to the display items, such as legends to figures, where international symbols were mistakenly replaced by odd character sequences (see, for instance, 1 μg instead of 1 microgram); b) the discussion, which turns around experiments that are not described in the paper, from previous studies by this author and by others, and which are not recapitulated in sufficient detail for the reader to understand how they help to reach the paper's conclusions. This is especially true of the discussions on cellular suppression mechanisms and high dose tolerance involving T and B cells. I also found it strange to read about how IL-4 suppresses IgG1 and IgE production, which may perhaps occur in specific conditions but goes against most reported studies, in which both Ig classes are dependent on IL-4 and enhanced by it. I respectfully recommend the author to give some attention to these issues, which would certainly help readers appreciate his experimental results, undoubtedly worthy of attention, even though the current version of the manuscript does not match current standards of English use and data presentation.

I have carried out research on development of monoclonal antibodies to cytokines in a different context. I have also been working in the field of immunoregulation by lipoxygenase products for over one decade. Although I have no direct experience in the production of anti-IL-4 antibodies, I am sufficiently familiar with the literature in the field to be able to point out a number of points in the paper that would benefit from further discussion, as well as changes that must be made in order to meet current publication standards. 

The work Immune Response of IL-4-Knockout Mice to Low-Dose Immunization with Autologous IL-4 by Vlaentin Schichkin is an original and interesting contribution to the field of immunology dealing with immunization in order to direct the immune response in specific situations.

I have been working in the field of lymphocyte develpment.

None.