I understand Th1/Th2 T cell polarization occurs in secondary lymphoid organs (e.g. lymphatic nodules), where T cells recognized the antigens in the presence of different signals that condition such polarization. Subsequently, the effector Th cells abandon the secondary lymphoid organs, reaching the tissues where they carry their function. What I would like to know is whether Th cells are completely committed to a particular phenotype (Th1 or Th2) when they reach the infected tissues or whether they still have a chance to change/modulate their phenotype “in situ”. A related question will be whether the effector phenotypes of Th cells (Th1, Th2, ...) are fixed or can interchange . Any help with this question will be appreciated.
Hi
I am also very interested in this point raised by Pedro. After reading the paper by Schneider and some others, I see the plasticity of these cells, however I am yet not sure about which will be the answer to Pedro´s question, i.e : Do Th commited cells still have a chance to change/modulate their phenotype “in situ” in in vivo conditions (upon cytokine exposure in the tissue).
That is the point. The conditions and cytokine milieu in the infected tissue are not necessarily the same than in the lymphatic nodules where Th1/Th2 differentiation occurs. These "in situ" conditions should affect/modulate the response of Th cells affecting their phenotype
Th1 and Th2 - are different cells (phenotype). Th1 can not become Th2, and Th2 can not become Th2. I understand you correctly? Various cytokines produce these cells.
It seems that Th1-Th2 cells may be modulated by the microenvironment, ie, cytokines. Pro inflamatory cytokines derived from damaged tissues affect their differentiation into Th1 or 2. It is also interesting that the route of antigen administration (cutaneous, iv, dermal) may influence the development of Th1 or 2. Experiments with Leishmaniasis regarding route of administration can induce Th1 or Th2 polarized immune responses.
You say that, depending on the microenvironment (cytokines) may emerge from Th0 Th1 or 2. (?) Yes, it is.
Dr. Zabrodskii my question goes on whether Th cells became fully committed in the lymphatic nodules (Th1, Th2 ..) –where they recognized the antigen and become effector T cells– or whether their phenotype can change o be modulated depending of the conditions that they encounter in situ the infected tissues.
Maybe they can become effector T cells. This is not described. I believe that Th1, Th2 can not change their phenotype. For that there are Th0-cells.
Dr Schneider, this is really very interesiting. Thank you very much!
That I could not even imagine. Effector T cells into Th2 cells? "It's interesting. Probably for increased production of B cells (plasma cells) IgE.
Dr Schneider, thanks for the reference. Very interesting indeed. So it seems that effector T cells can decide in situ their fate
Macrophages control Th1/Th2. Mills. J. Immunol. 2000. M1/M2 Macrophages
Hi Pedro,
I assume you are talking about mouse T cells in your question. As Dr. Schneider points out above, there is flexibility in the Th1/ Th2 phenotypes. A good paper you would enjoy reading is this: Immunity. 2010 Jan 29;32(1):116-28, where they describe how certain viral infections can alter the phenotype of committed Th2 cells in vivo by inducing the coexpression of T-bet and GATA-3 and expression of the corresponding cytokines. The mechanism described seems to involve effects of Type I and II IFNs and IL-12 on Th2 cells so yes cytokines are involved. Whether effector/ effector memory T cells are affected at the site of infection was not addressed in that paper but given the abundant levels of IFN-g and IL-12 at those sites I would guess that it could occur.
If you are referring to human T helper cells, it is harder to find true polarized human Th1/ Th2 phenotypes so your question would be harder to answer.
Dr. Hidalgo, my question was general but of course the interest is in human.
Dear Pedro
I have been working on infections diseases and indeed in humans and animal models the polarization is always observed. Helmints and bacteria can induce such polarization. Macrophages indeed participate on the polarization but depending on the pathogen other cells can also play a role on that. Among the effector cells you find the subgroup of Th0 that are actually the type of cell that can become Th1 or Th2 depending on the signaling of the microenvironment. It may happen that even when the immune response is polarized to Th2 for instance you do observe Th1, like in schistosomiasis. The polarization Th1/Th2 depends on the pathogen but in general both are present. The paradigm of total polarization is not anymore valid nowadays..it is becoming clear that both are present and this is necessary for the immune system to respond a any co-infection.
Dr. Zorzenon thanks for the insights.You are right. The Th1/Th2 is an oversimplification. However, my question was more on whether there is polarization changes, in situ, in the infection site, or it is all determined in the secondary lymphoid organs.
Dear Pedro
I would say that depends on the pathogen or the situation you are thinking about: for instance in TB it will take place mainly in the lungs, on schitosomiasis mainly on the liver, depending on the situation on the lymphoid tissues.
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