Regulation, FoxP3, Suppression and Immunity

It is exactly 50 years since the first of my predecessors in the editorial chair at Immunology, John Marrack, put pen to paper to write his opening editorial (Fig. 1).¹ At that time, fighting for a fledgling journal in an embryonic field, he was most exercised with what the new field and thus the journal would come to be called. ‘Immunology’, despite his concerns over its shockingly mongrel Latin–Greek roots, was favoured over ‘Immunity’ because the former described the science, the latter a physiological state. This was to become the first dedicated journal for immunologists after Journal of Immunology which had been in production in the USA from 1916. The early volumes of Immunology include seminal works in modern immunology from Nobel laureates and many of the other key thinkers of the period including Peter Medawar, John Humphrey, Baruj Benacerraf and Peter Gorer.

Figure 1.

Cover page of Immunology volume.

During the intervening 50 years there have of course been many key immunological contributions and debates in the journal involving major immunologists of the 20th and 21st centuries. One of the running themes that has straddled around 40 of the journal’s 50 years has been the issue of how the immune response achieves appropriate regulation. While the concept of tolerance had been in circulation for decades, the publication of a paper in this journal by Gershon and Kondo in 1970 signalled the beginning of immunological thinking about active, cell-mediated suppression/regulation and the underlying mechanisms.² That publication has since been much cited and in-favour, then following the years of the major histocompatibility complex I-J debacle, deeply out of favour, and is now again frequently cited. The rise and fall of the years of T suppressor (Ts) cell immunology have been followed by a period when more robust technologies allowed immune control to be described in relative molecular detail through the functions of regulatory T cells (Treg), including many significant contributions in this journal relating to normal function and disease.^3–10

It occurred to us that a fitting way to mark the 50th anniversary of Immunology would be to invite key players in this field to offer us their analysis of where we have come to in the field of regulation. While we used the Ts paper as a springboard and invited the contributors to comment, if they wished, about the relationship between the Ts and Treg phenomena, they had free rein to interpret the brief either with this historical sweep, or purely in terms of current research, or indeed in terms of personal reminiscence. With respect to the historical perspective, there was no revisionist agenda either to resurrect or vilify the earlier generation of work on regulation; rather, a sense that it may be fitting to pause and ponder how we got to where we are now and what we can learn about how to shape our future research. We are honoured that a team as eminent as Tony Basten, Barbara Fazekas de St Groth, Ron Germain, Mark Greene, Ana Izcue, Judith Kapp, Tom Lehner, Bin Li, Fiona Powrie, Ethan Shevach, Liz Simpson and Herman Waldmann took up the gauntlet.^11–19 We hope you will enjoy reading their views on this subject.