"OKT3, OKT4 and all that" 2 September 2004
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Eleni Papadopulos-Eleopulos,
Biophysicist
Department of Medical Physics, Royal Perth Hospital, Western Australia, 6001,
Valendar F Turner, John Papadimitriou, Barry Page, David Causer, Helman Alfonso, Sam Mhlongo, Todd Miller, Christian Fiala

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Re: "OKT3, OKT4 and all that"

"OKT3, OKT4 and all that"

In his rapid response: "Re: "HIV" and KS, 18 August, Nicholas Bennett wrote: "I'm amazed at their use of a single speculative paper from 1983 calling into question whether the T cell "marker" of T4 is in fact functional. This is crazy!"

In their 1983 paper entitled "Phenotypic diversity within clones of human normal T cells"1Zagury and his colleagues selected normal human T cells for in vitro cloning according to the expression of T4, T8 or T10 antigens on individual cells. They reported that:

(a) "Clones were produced from each of these cells irrespective of the antigenic phenotype of the parental cell. The cloned progeny manifested, in many cases, shifts in antigen expression. Thus, T4+T8- cells have clones expressing predominantly T4-T8+ and vice versa. The clonal expression of T4 and T8 seemed to be mutually exclusive. Antigenic shifts were recorded also in clones derived from T4-T8-T10- cells, resulting in T10+ clones which were also either T4+ or T8+ and from T4+T8-T10+ cloned cells yielding clones of either T4+ or T8+ cells."

The phenotypic changes of T4 to T8 and vice versa has been reported by other researchers2 3Montagnier (and most probably Gallo, since Zagury was one of his collaborators) was aware of this phenomenon.

In 1984 he wrote that the decrease of T4 cells in "HIV" infected cultures is "probably due to either modulation of T4 molecules at the cell membrane or steric hindrance of antibody=binding sites".4 5

Thus at the beginning of the AIDS/HIV era, some of the best experts were aware that a decrease in T4 cells may not mean T4 cell death but simply a change of T4 into T8.

(b) "Testing functional properties we found that NK activity was mediated not only by T10+ cells but also, in some cases, by T4+ and T8+ cells. Moreover, TCGF production, which may reflect helper activity, was mediated not only by T4+ cells. Only the cytotoxic (CTL) activity seems to be confined to the T8 phenotype. Thus, it appears that T antigens, which seemed to be molecular markers of differentiation, are not markers for terminal differentiation and do not always reflect defined functional properties".

In an editorial in the Scandanavian Journal of Immunology in 1988 Göran Möller from the Department of Immunology, University of Stockholm wrote: "There are three good and several not so good reasons for questioning the existence of suppressor T cells as a separate T cell subpopulation".6

Commenting on Möller's editorial researchers from the Pasteur Institute wrote: "It follows that the difference between these two cell populations concerns their repertoires and, in consequence, their maturative or activation stages, possibly their differential mechanisms of activation....As discussed here, even primary populations of lymphocytes may follow functional rules in vitro that depart substantially from those operating in vivo, and cells may look and function differently simply because they are either connected or isolated. In essence, and this is both more interesting and difficult to approach, it seems unavoidable that systems (such as the immune) are more than the sum of isolated clonal activities".7

In a 1981 commentary in JAMA entitled: "OKT3, OKT4, and all that", one reads: "The T- and B-cell measurers-having run through the sick, the elderly, the young, the pregnant, the bereaved-had finally run out of diseases. Each condition was the subject of many reports; so that now, to give but one example, we can conclude with some assurance that T-cell numbers are up, down, or unchanged in old folks….And now it's starting all over again, this time with T-cell subsets. Think, dear reader, and grieve, dear editor, about how many investigators are at this very moment measuring T-cell subsets in systemic lupus erythematosus, in rheumatoid arthritis, in solid tumours (all different sorts - one article for each), in lymphomas, in pneumonia, after surgery, after burns, after trauma, in asthma, in cirrhosis, in Crohn's disease, in glomerulonephritis, in myositis, in familial Mediterranean fever, in leprosy, in Dengue fever, after cardiac transplants, and so on. Meanwhile others will be out measuring blacks, whites, Orientals, native Americans, men, women, children, babies, old folk, astronauts, and laboratory technicians. Cells will be garnered and measured from blood, from lungs, from kidneys, from liver, and from CSF and ascitic fluid….What can be done to stanch the anticipated outflow?….We might legitimately ask, why fight? Why not let us unimaginative immunologists publish to our heart's content? I will ignore the obvious economic arguments for fear that they might be taken seriously. My strongest argument is this: Measurement of T and B cells and their subsets in diseases has no clinical meaning….There is a feeling about that T- and B-cell numbers mean something, an immunologic equivalent of an SGOT level or creatinine clearance…Nonimmunologists have naturally assumed that any subject occupying so much journal space must be relevant in some way – a logical but incorrect assumption".8

That measurement of T cells "subsets in diseases has no clinical meaning" is best illustrated by the evidence which accumulated in the AIDS era.

By definition T4 cells helps B cells to produce immunoglobulin, hence their name, T helper cells. According to the "HIV" experts, "HIV" kills the T4 cells, the helper cells. If the T4 cells have a helper function, then all AIDS patients must have hypogammaglobulinaemia (low antibody levels). However, one of the main laboratory findings in AIDS patients is hypergammaglobulinaemia.

According to the "HIV" experts the diseases which constitute the acquired immune deficiency syndrome, the S in AIDS, are the consequence of the low T4 cell number, (AID), induced by "HIV".

However, according to the same experts these diseases continue to appear even after HAART induces "immune restoration" and decreases of the "viral load" even to non-detectable levels.

Since the AIDS indicator diseases appear after HAART "suppression of HIV viraemia" and "immune reconstitution", the only conclusion one can draw is that neither "HIV" nor the T4 cells are causally related to these diseases. Instead of coming to these obvious conclusions, the AIDS/"HIV" experts simply gave these diseases a new name: "Immune Restoration Disease (IRD)".9 This means that one and the same disease in the same individual before HAART treatment in the presence of low T4 cells and high "viral load" is an AIDS disease. After "Suppression of HIV viraemia" and "immune reconstitution" by HAART, the disease is IRD and the patient dies from "immune restoration disease", not AIDS.

According to the AIDS/"HIV" experts: "Differentiation of IRD from an opportunistic infection is important because IRD indicates a successful, albeit undesirable, effect of HAART".9

The question is, what does "successful" mean and what is its clinical relevance?

1. Zagury D, Bernard J, Morgan DA, Fouchard M, Feldman M. Phenotypic Diversity within Clones of Human Normal T Cells. Internat J Cancer 1983;31:705-710.

2. Birch RE, Rosenthal AK, Polmar SH. Pharmacological modification of immunoregulatory T lymphocytes. II. Modulation of T lymphocyte cell surface characteristics. Clin Exp Immunol 1982;48:231-238.

3. Burns GF, Battye FL, Goldstein G. Surface Antigen Changes Occurring in Short-Term Cultures of Activated Human T Lymphocytes: Analysis by Flow Cytometry. Cell Immunol 1982;71:12-26.

4. Klatzmann D, Barré-Sinoussi F, Nugeyre MT. Selective Tropism of Lymphadenopathy Associated Virus (LAV) for Helper-Inducer T Lymphocytes. Science 1984;225:59-63.

5. Klatzmann D, Champagne E, Chamaret S, Gruest J, Guetard D, Hercend T, et al. T-lymphocytes T4 molecule behaves as the receptor for human retrovirus LAV. Nature 1984;312:767-768.

6. Moller G. Do suppressor T cells exist? Scand J Immunol 1988;27:247-50.

7. Pereira P, Larrson-Sciard EL, Coutinho A, Bandeira A. Suppressor versus cytolytic CD8+ T lymphocytes: where are the artefacts? Scand J Immunol 1988;27:625-627.

8. Goodwin JG. OKT3, OKT4, and all that. J Am Med Assoc 1981;246:947-948.

9. French MA, Price P, Stone SF. Immune restoration disease after antiretroviral therapy. AIDS 2004;18:1615-27.

Competing interests: None declared