Lymphokine nomenclature

Immunology Today, Vol. 9, No. 12, 1988

support than ever. How sad it is for the .(>.-eatlight that illuminated, enerhis students, colleagues and friends gized and enchanted our lives should the world over that, at such a rime, have been so wantonly extinguished.

* From the International Union of Immunological Societies, Nomenclature Committee, Working group on lymphokines.

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One of the most impressive achievements in the study of the regulation of growth and differentiation of cells of hematopoietic lineage has been the discover, purification, cloning and f:mctional characterization of a series of secreted regulatory proteins (cytokines), many of which are produced by T lymphocytes. These molecules play critical roles in many normal physiological responses, have clear pathophysiological significance and are certain to have importance as therapeutic agents. Unfortunately, because of the large number of distinct proteins of this type, considerable confusion exists regarding their individual functions. Furthermore, the names of many of the proteins are such that the nonspecialist is often uncertain as to the identity of a factor with a particular designation. Table 1 lists a group of the secreted regulatory proteins that act on cells of the lymphohematopoietic system. Several scientific organizations including the International Union of Immunological Societies (IUIS) have become concerned with the difficulties that are presented by the plethora of distinct 'lymphohematic' regulatory proteins and the lack of standard names for many of them. It is anticipated that these problems will become more serious as new factors are discovered and characterized and as new functions for existing regulatory proteins are recognized. Dr K. Frank Austen, chairman of the nomenclature committee of the IUIS, has asked me to convene a group of scientists to discuss what, if anything, should be done regarding the development of an agreed-upon naming system for the current lymphokines, hematopoietic growth factors and related molecules and for similar regulatory proteins that remain to be discovered and characterized. I write at this time to solicit opinions about this issue. In particular, I

J. Hall is in the Section of Tumour Immunology, TheICRRoyalCancerHospital,Sutton SM2 5PX,UK.

-,l'"nhol"ne nomenclature from William E. Paul would be interested in comments (6) Would you favor renaming regarding the following points: any existing factors or would you (1) Do you believe there is a limit application of any guidelines to problem? newly discovered molecules? (2) If a problem exists, should the (7) Would a code system, such as IUIS or a comparable body attempt that used to name enzymes, be to develop a standardized naming useful? system? My own view is that if an 'official (3) If so, how broad should the nomenclature' system is deemed effort be; should it be limited to the advisable, an 'official' name should lymphokines and the hematopoietic not be 'issued' until a molecule is growth factors or should it encom- very well characterized. Before an pass a broader array ef such mol- official name is issued, a new cytoecules (e.g. platelet-derived growth kine should be known simply by a factor, insulin, etc.)? name (or names) proposed by those (4) Who should participate in a using it. Preferably that name, and group convened to discuss this any subsequently adopted official issue? In particular, if a naming sys- name, should convey some functiontem is envisaged for a broad range al property of the molecule and of factors, what other scientific or- should not be one that simply exganizations should become involved tended an already existing series of in the process? names, such as 'interleukin 15'. The (5) Should there be small sub- latter point is of some importance groups to consider each of the mol- since the interleukin names carry no ecules independently? inforrnation whatever about the regulatory functions of the protein and thus are not helpful in attempto remember what the molecule Table1. Somesecretedregulatoryproteins ting does. Furthermore, the interleukin of the 'lymphohematicsystem' (incomplete designation appears to be 'official' list) by its very nature but such names have usually been unilaterally interleukin2 (IL-2)(T-c~llgrowthfactor) adopted by individual groups. InInterleukin4 (IL-4)(B-cellstimulat0ryfactor-I) deed, there have been occasions Interleukin5 (IL-5)(B-cellgrowthfactor-II) when the same interleukin name Interferon-gamma(IFN-~/) was proposed for several distinct Lymphotoxin(LT) molecules, leading to censiderable confusion. Interleukin3 (IL-3) It seems likely that small working Granulocyte-macrophagecolony-stimulating groups will have to be set up to factor (GM-CSF) Granulocytecolony-stimulatingfactor(G-CSF) develop agreed-upon r.~mes for those cytokines for which there is Colony-stimulatingfactor-1(M-CSF) lack of unanimity about "::he approInterleukin1 (IL-1) priate designation. Such names Tumornecrosisfactor(TNF) would then be submitted to the IUIS Transforminggrowthfactor-beta(TGF-13) with a recommendation that they Interleukin6 (B-celldifferentiationfactor, should be given official status. It hybridomagrowthfactor,hepatocytewould seem unwise to change any stimulatingfactor, interferon132,etc.) existing name that has received wide Lymphopoietin1(interleukin7) acceptance, including the widely used interleukin designations, unless Neuroleukin there was a consensus among those 1988, ElsevierSciencePublishers Ltd, UK 0167 49191881502.00

ImmunologyToday,Vol. 9, No. 12, 1988

in the field that a new 'official' name would be useful. That leaves the problem of how official names and preliminary names would be distinguished from one another. One approach that has appealed to me is that the official designation would include not only the agreed upon name of the cytokine but also an official descriptor consisting of the letters SR for 'secreted cell-regulatory protein' or 'secretory regulin' and a number. If this approach were used, SR designations would also be issued to cytokines that have names that are now widely accepted. For example, IL-1 might carry the descriptor SR-1. It would be most useful if, at the time of first use in any paper, both the official name and official descriptor appeared (i.e. interleukin-1 (SR-

I should also point out that this naming system would be sufficiently general to be used for all secreted cell-regulatory proteins and need not be limited to lymphokines ar~.d related molecules. I know how serious the resistance will be to a new nomenclature system, but it seems to me that the lack of any recognized standards for naming current or new factors has led to confusion even among those active in the field; for outsiders, the problem is clearly worse. In addition, clarification of the nomenclature problem niight be of particular value in accessing the growing bibliographic, nucleic acid and protein databases, in which confusion about the naming of a molecule sometimes makes obtaining information difficult. Finally, I suspect that many more regulatory proteins remain to

be discovered so that wise action now may forestall even greater confusion in the future. I would be very grateful for opinions on this matter and particularly for views regarding whether an effort should be made to achieve a unified system of 'official' designations. It would be most helpful if such responses could be sent as quickly as possible. Those who wish to participate further in this process should let me know. Finally, please make interested colleagues aware of this letter. We wish to have the broadest input into determining the best course of action.

o~ and the other the 13 transgene. They were obtained by co-injection of both transgenes into fertilized eggs. (2) Tolerance in male mice was not measured by loss of transgene expressing (F23.1 +) T cells but by lack of autoreactivity. The fact is that male transgenic mice that are tolerant to male antigen nev~r~neless ........... have plenty of transgenic receptorexpressing T cells which do not express CD4 or CD8 accessory molecules. Most of the data I presented have now been published ~,2, and the

interested reader is asked to look into these papers for a complete account of our results.

erties of each subset supports the notion that the TH1 and TH2 subsets actually comprise subsets within the CD4+4B4+(2H4 -) population. First, studies by Rudd and coSir, Recently, Bottomly and co-workers workers show that the CD4+2H4 +/(ImmunoL Today 1988, 9, 268-274) subsets can be distinguished by the have postulated that the human differential expression of time T200 CD4+2H4 + and CD4+2H4 - subsets 200•220 kDa isoforms on the are the human counterparts of the CD4+2H4 ÷ subset. In contrast the murine TH1 and TH2 subsets ~. In CD4÷2H4 - subset is restricted in part, the correlation is based on the its expression of the 180/190 kDa observation that 'the CD45R low isoforms 2 Extending this analysis to density or negative subsets provides T200 expression on TH1 and TH2 effective help to B cells'. Although clones, we have recently found that this appears consistent with their both types of clones express only the hypothesis, I believe that a more isoforms at 170-190 kDa, which detailed examination of the prop- places these subsets within the

CD4+4B4+(2H4 -) subset (C. Rudd, S. Helms, M. Dorf and S. Schlossman J. Exp. Med., submitted). Second, in terms of lymphokine production, TH1 cells produce IL-2, lymphotoxin and gamma-interferon, whereas the TH2 subset produces IL-4. In contrast, both the CD4+2H4 + and CD4+2H4 - subsets can produce both IL-2 and gammainterferon (T. Takeuchi and C. Morimote, unpublished). Thus, while still subjudice, these data suggest that the CD4+2H4 ÷1- subsets are not the human analogues of the murine TH1 and TH2 subsets. Lastly, there is a need to be more discriminating in the use of the term

i)).

The true function of the thymus Sir, In their recent meeting report (Immunol. Today, 1988, 9, 189-193), M. A. Ritter, J. Rozing and M. J. Schuurman included in the section ............... ~,. .... mlce a summary of my talk that contained two inaccuracies. (1) T-cell receptor transgenic mice were not created as an F1 cross between two parental transgenic strains, one of which possessed the

A functional dichotomy in CD4÷ T lymphocytes

(~ 1988, ElsevierSciencePubhshersLtd, UK 0167-4919/88/$02.00

Pleasereplyto W.EPaul,BldgfORmIIN311, NationalInstitutesof Health, Bethesda,MD 20892, USA;telephonenumber:(301)496 5046:FAXnumber:(301)4960222.

Pawel Kisielow TheInstituteof Immunologyand Experimental Therapy,PolishAcademyof Sciences, Uili ULIGIW, FUI~IIU.

References

1 Kisielow,P., BIUthman,H., Staerz,U., Steinmetz, M. and Von Boehmer, H. (1988) Nature 333, 742-746 2 BIQthman,H. etal. Nature (in press)

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