Along the Axis between Type 1 and Type 2 Immunity; Principles Conserved in Evolution from Fish to Mammals

A phenomenon already discovered more than 25 years ago is the possibility of naïve helper T cells to polarize into TH1 or TH2 populations. In a simplified model, these polarizations occur at opposite ends of an “immune 1-2 axis” (i1-i2 axis) of possible conditions. Additional polarizations of helper/regulatory T cells were discovered later, such as for example TH17 and Treg phenotypes; although these polarizations are not selected by the axis-end conditions, they are affected by i1-i2 axis factors, and may retain more potential for change than the relatively stable TH1 and TH2 phenotypes. I1-i2 axis conditions are also relevant for polarizations of other types of leukocytes, such as for example macrophages. Tissue milieus with “type 1 immunity” (“i1”) are biased towards cell-mediated cytotoxicity, while the term “type 2 immunity” (“i2”) is used for a variety of conditions which have in common that they inhibit type 1 immunity. The immune milieus of some tissues, like the gills in fish and the uterus in pregnant mammals, probably are skewed towards type 2 immunity. An i2-skewed milieu is also created by many tumors, which allows them to escape eradication by type 1 immunity. In this review we compare a number of i1-i2 axis factors between fish and mammals, and conclude that several principles of the i1-i2 axis system seem to be ancient and shared between all classes of jawed vertebrates. Furthermore, the present study is the first to identify a canonical TH2 cytokine locus in a bony fish, namely spotted gar, in the sense that it includes RAD50 and bona fide genes of both IL-4/13 and IL-3/ IL-5/GM-CSF families.