Talk:T helper cell

Image is misleading and many pages have it

The title image is misleading. The processing of becoming a CD4 or CD8 cell occurs in the thymus prior to puberty during development. A person logging on to this page will think that this process occurs normally. It does not. Once cells are in the periphery, they are either CD4 and CD8 and do not change (as far as I know).

I chased up and looked at the reference. The image in the provided reference for the image has been substantially edited The arrows and most of the words have been added by whoever uploaded it. M0rt (talk) 05:53, 31 May 2009 (UTC)

I think it's very important that this issue is cleared up ASAP. Many pages have this misleading diagram. M0rt (talk) 05:53, 31 May 2009 (UTC)

Th17

There isn't even a mention of Th17 cells on here. I don't know enough about them to write it myself, anyone know more? They are mentioned in the interleukin 23 article. 88.111.4.45 19:02, 27 January 2007 (UTC)

"Welcome.. Welcome to City 17.." oh.. wrong article.. You're writing it like there's a huge omission. These cells are obviously new onto the scene, or at least, mainstream immunology. Whoever has written Interleukin 17 has put a bit of effort into that article. When I focus on it, the articles mention the fact that helper cells exist, but give NO detail about how it works. Is it just because they produce IL-17? My guess is that Th17 cells active various portions of both Th1 and Th2, and obviously, produce IL-17. If it has a full feedback mechanism against Th1 or Th2, then i'd be very interested. My guess is that IL-23 induces IL-17 which just turns everything.. well not everything.. but a lot of things.. on. I've read articles for about 8 years suggesting that the Th1/2 definitions don't exist in individual cells, and that most cells express all sorts of cytokines and therefore could do all sorts of things (there is a publication by Kelso et al that demonstrated this with single cell RT-PCR). I do wonder if this is a new combination that's just one of the many many individual ones, that happens to come from IL-23 exposure. Even though I'm a skeptic, I haven't read about it. I could be completely wrong. Maybe it's just because if I had my way, I'd axe the whole "Th" wording. It's a good basic concept to teach students, but researchers need to start coming up with a better way of defining Th cells, based on function behaviour. Not just (1) measure whatever their most prevailent cytokine is, (2) associate cytokine with known effects, which is where we (and that IL-17 article) is at. The real challenge is to take what we know from these cytokine systems, throw in all the mechanisms, and apply it in vivo... oh, and then cure the world of everything :)Volantares 23:44, 9 February 2007 (UTC)

A cell produces either IL-4 or IFN-gamma or IL-17 - you don't generally find any cells expressing combinations of those cytokines in vivo or in vitro, that much is true about the Th1/Th2 paradigm. Th17 cells are generated using TGF-beta and IL-6 and sustained by IL-23 - you can show that both in vitro and in vivo. They are crucial for defence against some intracellular bacteria and may cause several autoimmune diseases (they've been described as essential in EAE, a mouse model of MS). I'll write something on Th17s.

While I haven't kept close contact of the Th model for a few years, you may find this article interesting: Kelso A. Groves P. Ramm L. Doyle AG. Single-cell analysis by RT-PCR reveals differential expression of multiple type 1 and 2 cytokine genes among cells within polarized CD4+ T cell populations. International Immunology. 11(4):617-21, 1999 Apr. To quote the abstract "However, most cells expressed only none to three of the six cytokines assayed, few displayed the canonical type 1 profile and none in either response expressed a full type 2 or type 0 profile.". Unless someone can produce an article that debunks this finding and proves that individual helper T cells follow the Th1/Th2 pattern, I believe that the Th1/Th2 model is more a profile of a T cell population, and not of individual cells. Perhaps this needs to be clarified in the article, and that reference obviously needs to be put in at some point.Volantares 20:03, 11 April 2007 (UTC)

I think the general feeling is that the Th1/2 model reflects normal distributions in populations generated in response to certain stimuli. The interesections of these distributions give us cells which appear to cross the "boundries" when in fact no actual firm boundries exist- just tendencies. On that reference, cell-by-cell analysis can be misleading, particularly when the measure is RNA rather than protein. I think the model is still good as a general desciption but requires the addition of Th17 etc. The simple 1/2 model is not really taught anymore in my (admittedly limited) experience. Anyway I have started a Th17 article, based on what I know. Perhaps it needs to be merged with this article but personally I'd rather see dedicated small articles on the various elements of the Th model rather than the one quite bloated article we have now. DoktorDec 12:50, 2 October 2007 (UTC)

The author who started this thread is right. It's a huge omission to discuss Th1/2 and not discuss Th17. The old Th1/2 paradigm isn't accurate anymore. A lot of the other comments about why to not include Th17 are just people's opinions, and I don't believe they reflect what's in the literature. For a really good review of the history of how the Th1/2 paradigm was phased out and replaced with the Th1/2/17 paradigm read Lawrence Steinman's review in Nature Medicine (Volume 13, No. 2, Feb 2007). DoktorDec, I know this article is a little "bloated," but I think it would benefit from being merged with your Th17 article. Txh190 15:41, 6 June 2008 (UTC)

That may be the case. I would still hold that the current article could benefit from being briefer and more approachable with separate articles dealing with the core concepts in more detail. Much of what is presently in the article is more detailed than an encyclopedic article perhaps demands. DoktorDec (talk) 20:26, 6 June 2008 (UTC)

Yeah, I agree. Too many hands in the kitchen... Txh190 20:19, 7 June 2008 (UTC)

I'd like to suggest a re-organisation of this page - remove the activation section - it'd be better on the T cell page - to mainly focus on Th1/Th2/Th17 differentiation. Th3 isn't a terminology used anymore - TGF-beta skewed T-helper cells are bona fide Foxp3-expressing Tregs. It might also be better to start a "T cells in HIV" page, as it's a specialist area Kantokano 09:49, 28 February 2007 (UTC)

The reason why this article has an activation section is because there have significant inconsistencies between T cell articles, and I believe it is important to emphasise the differences in the activation of different T cell groups, especially the role of IL-2 (and its source) in T cells. Perhaps the section can be reduced or removed, but only if the parent article completely picks up the slack. I've intended to sit down and try and do this, but I haven't had the time. As far as getting rid of Th3; if it is out of date then go for it. The diseases section, is in its infancy as far as intention was concerned. I had intended to briefly give specific content discussing the particular roles of helper T cells in pathogenesis/disease. At the moment it's very much a Th broken record. I was hoping that section would diversify, not disappear. Creating unique articles for such information will not always be justified. I see no problem in creating a more specific article that focuses in more detail on the role of T cells in HIV, and I'm currently not in a position to create a significant article in this regard without quite a bit of research. I do not see a reason why HIV cannot be summarised with some detail in this article considering it will be directly and legitimately linked from the HIV article along with other related articles.Volantares 20:03, 11 April 2007 (UTC)

It seems this discussion is getting away from the central point -- whether or not enough evidence of the exclusive differentiation of Th17 cells is conclusive enough and encyclopedic enough to warrant mention here -- especially since this article seems to be the central reference to the Th1/Th2 model anywhere in the immunology topics. Independent data from the laboratories of Cua, Stockinger, Weaver and Kuchroo, respectively, all seem to support Th17 cells as a unique and distinct CD4+ lineage, alongside Th1s and Th2s. I'd definitely argue that it warrants inclusion, given careful qualification.

Volantares, the exclusive polarization of CD4+ cells to Th1 and Th2 has always been problematic [i]in vivo[/i] -- historically, truly exclusive polarization (most often, cytometrically) is mostly seen in clonal systems, often in vitro. I haven't had a chance yet to look at the International Immunology reference, but I don't find it surprising. Rather than get into a debate over the physiologic relevance of the Th1/Th2 model, I can only point out that, incorrect or incomplete as it may be, the Th1/Th2 model has dominated immunology for two decades. It may be overly reductionistic, but that's why it's only a model. Addressing the problems of Th1/Th2 is definitely encyclopedic, but only if it doesn't outweigh what researchers have been able to demonstrate within that model.

As to addressing the 'Activation' problem -- it frankly falls much more under T cell than it does here. It seems a misprioritization for the discussion of costimulation to be more succinct there, than it is here. Jbarin 06:42, 8 May 2007 (UTC)

The activation section can be written and co-ordinated more effectively in the T cell article. It just requires consistency, although I haven't checked that article for a short while. While that is in my head, should the concept of Th0 be included (if it is not obselete)? As far as including Th17 is concerned, I think that if Th17 is mentioned regularly at the review level, then its inclusion in some form is justified.Volantares 17:11, 13 May 2007 (UTC)

Th0 is worthwhile mentioning, although it seems to be falling out of favor as a preferred terminology. Nothing quite so catchy has stepped up to replace it - it seems that 'mature, uncommitted precursor' may be unwieldy. Th0 sums that up reasonably well, as Th1 stands in for "T-bet-committed, IFNγがんま-producing", and so forth. Th17 is in since last I visited, as are IL9-producing Th9 cells. The recent proliferation of CD4+ subsets to include follicular helper T cells, alternative regulatory T cell populations - the list is getting rather crowded quite fast. Jbarin (talk) 21:38, 27 October 2010 (UTC)

The direct associations between CD proteins and cell function probably should probably not exist, but rather the two should be strongly linked. There are exceptions to these rules, e.g. CD4+ cytotoxic T cells exist.

Huh?

Almost pure technobabble. I think Wikipedia should be more accessible to the general public, don't you?

I've rewritten most of the page. I hope this is a little more easy to read. A lot more could be done, but at the moment some sections of the immune system on Wiki is quite good, others are woeful. If you're able to contribute, or have comments, you're welcome to do so. Volantares 11:25, 1 October 2005 (UTC)

Great, so now its so easy to read that its misleading... This article needs quite a comprehensive rejig... I'll do it when i got the time :-) (User:AnonymousCoward)

There is a division between what the scientific community wants in a wiki entry and what the general public might need to know. Therefore there should be separate articles to serve each type of reader.

i am a student trying to learn about this subect so i am unable to present any solutions to this problem but i would like to point out that there is alot of usless info in here that makes it confusing. eg. "They also appear to make occasional mistakes, or generate responses that would be politely considered non-beneficial. In the worst case scenario, the helper T cell response could lead to a disaster and the fatality of the host. Fortunately this is a very rare occurrence." this is completely off topic and seems to be i place of actual info on the roll of T helper cells.

there is currently no actual explination of what they do, jsut 2 explinations on how they react/act under specific situations that are not particularly important. there is alot of perfectly useful info in the article but it seems to be dancing around the real meat and potatos info about what they actualy do. maybe its better suited to somone who already knows about this topic. im not having a crack at the author jsut hough it might be helpfull to hear what a less educated person needs in a teaching article. also i dont think there needs to be 2 articles. there should be no reason why simple expinations and complex information about the realy detailed things cant be incorperated into the one article. maybe after the simple explination, the complex info might make sence to even uneducated people. 124.190.3.146 17:11, 17 June 2007 (UTC)

T_H model

I think we should still keep a seperate link to a more detailed T_H1 and T_H2 model page, due to the fact that the basic "type 1" and "type 2" concept is dated. For example, there are the proposed T_H0 and T_H3 sub-groups (although personally I'm weary of the proposals), but more importantly there is good evidence to suggest that during an in vivo response only a small percentage of T cells express cytokines of only one type (even if you exclude IL-2). The original model was based on hyperstimulated T cell lines, and therefore I see no reason not to highlight its limitations in a more technical page. The model was considered a breakthrough in how we see T cell responses, but there is MUCH more to the story than what is taught in third year university courses. I intend to write a seperate article on it at some point, but someone else is more than welcome to write it.

I think we also have to be very weary on a 20 year old "T_H1 = macrophages, T_H2 = B cells" mentality. That doesn't mean that it holds no merit, but it means that we have to be smart about how we write about this subject, because it is easy to over-simply the phenomenon. Volantares 09:49, 14 October 2005 (UTC)

Any input?

I don't think anyone reads this page, but I don't agree with the suggestion that Th1 cytokines produce auto-immune disease, while Th2 doesn't. It depends on the TYPE of auto-immunity: systemic lupus erythematosus has been associated with IL-4 (e.g. ref: Annals of the Rheumatic Diseases 2002;61:91-92) and I have some confidence that other antibody based autoimmunity is similar in mechanics. 59.167.10.179 13:42, 16 March 2006 (UTC)

After years of evidence to the contrary (interferon-gamma-deficient animals develop more severe organ-specific autoimmune diseases, for instance), a substantial portion of research still believe Th1-polarized cells potentiate organ-specific autoimmune pathology. The new Th17 story seems to clarify some of that, but I'll easily grant that "Th1 = autoimmunity" thinking is probably at least as overly reductionist as the Th1/Th2 model itself. Jbarin 07:28, 8 May 2007 (UTC)

This page gets about 1,000 page views a day. http://stats.grok.se/en/latest/T_helper_cell -- Nbauman (talk) 01:51, 11 November 2011 (UTC)

Count

I don't know if there's anything on a count, but I did a quick scan for a number and found nothing. I know off the top of my head an average for a non-infected HIV/AIDS person is 500 to 1500 T cells for every cubic millimeter. And I searched something and found it drops roughly 50 to 100 each year with the virus. So maybe that can be added? Here's the link for reference. I dunno. It's on so many pages, varying only slightly between 400 and 500 or so, so it's definitely note-worthy. I'm just scared to put it in.-Babylon pride 18:22, 21 January 2007 (UTC)

Just found out the count is mentioned on HIV Test but not here. Considering this is the main article and not just a random section, I'm just figuring...-Babylon pride 01:53, 22 January 2007 (UTC)

Feel free to put it into the HIV section, although try and make it fit in with the rest of the section. If worst comes to worst, we'll just adjust it to read better. I do a lot of editing on this page and I try not to change things other people put in unless it's wrong, or it's already been said, or some other reason. Occassionally I may re-arrange things, but it's an open encyclopedia and everyone is working together to make it as good as possible. I think you should also ensure that there is a page which lists the immune cells present in different parts of the body, or at least blood, and their counts/percentages. I haven't seen one but I also haven't looked. I'm trying to finish a few things, then plan on referencing this article, before I go onto others.. my next aim may be to make the T helper/cytotoxic T cell/T cell articles consistent with each other in regards to locations of subjects, and consistency in things like activation, as the cytotoxic T cell version does not quite match what I was taught and have read. I'm sure there are people who are closer in research than I in that regard though.Volantares 12:10, 22 January 2007 (UTC)

chocolate rose is super duper cool :p

look at the end of this sentence...

There are also other types of T cells that can also influence the expression and activation of helper T cells, such as natural suppressor T cells, along with less common cytokine profiles such as the Th3 subset of helper T cells. in "Complexities surpassing the Th model"

does anyone gets the meaning??

I think I do. It is awkward though -- I'll give it a quick lookover for language. It looks like this section may be undergoing substantial revision and reorganization in the foreseable future, though. Jbarin 06:45, 8 May 2007 (UTC)

Okay, the IL10 story is unnecessary -- IL10's long been moved out of the Th2 category12; despite the fact that early work described IL10 being Th2-associated -- it's still problematic that IL10 expression seems to be GATA3-dependent, suggesting the possibility that it's not so much a Th2 cytokine, as it is generally suppressive.

The discussion of T helper subsets switching from effector to suppressive phenotypes is out in the literature, but it also treads awfully close to WP:NOR -- especially, given that the text makes it sound like an effector Th1 or Th2 cell becomes a Regulatory T cell (also in the literature, but hardly conclusive).

I'm also switching out "Suppressor T" for "Regulatory T", since it winds up redirecting to "Regulatory T cell", anyways. An unfortunate semantic.

Also, can we talk about coming to a consensus about the subscripting tags in the "Th1"/"T_H2"? It seems problematic. If I recall from the original Mosmann & Coffman, "T_H" was the preferred construction. "T_h" is probably the least correct -- since the lower-case was only used as an expedient for older publication and printing systems in which extensive subscripting or small-caps'ing wasn't economical. I'd actually vote for doing away with the subscripting on that term altogether. Jbarin 07:24, 8 May 2007 (UTC)

That whole section was written to point out that the model does not match the reality, and I wasn't the best person to write it. Some of it is obselete (as pointed out), because I've been away from the field for many years for unfortunate reasons. I hope to dip my toe into the water again soon. I will not give a specific vote yet, but I think it would be logical to mimic whatever is currently written on the relevant reviews. Can someone verify what is typically used, and then I'll vote. PS It's nice to see that the page is getting the attention that's needed. I had always procrastinated doing the same.121.44.39.68 16:51, 13 May 2007 (UTC)

we have two of the same page only slightly different

lets merge them or eliminate one. here they are...

http://en.wikipedia.org/wiki/Helper_T_cell and http://en.wikipedia.org/wiki/T_helper_cell i think the first is more comprehensive, but the chart on the second is good. Brendan19 06:16, 11 May 2007 (UTC)

Doesn't one link to the other? Something strange is going on, though. I'd actually prefer the "parent" page as Helper_T_cell, and T_helper_cell linked to it, rather than it way it is now. Vote if you wish.121.44.39.68 16:41, 13 May 2007 (UTC)

correction, something strange WAS going on. there were two very similar articles. one had a few more paragraphs of info than the other/current article. after i suggested a merge there appeared to only be one article. i cant find the other anywhere. hopefully this article will grow in size to be more comparable to the other one or maybe someone can figure out where the other lost article is and add it here. Brendan19 09:07, 14 May 2007 (UTC)

Looks like no-one found the old Helper_T-cell article. Rod57 (talk) 14:06, 26 September 2010 (UTC)

TGF-beta

It seems that TGF-beta is considered in the broader context as a Th2 cytokine along with IL-10 see PMID 11121511 which is in conflict with the text of the Article. Can someone clarify for me, so that I can link to this site with some certainty? Jagra (talk) 03:59, 23 February 2008 (UTC)

Bit of an old review - it pre-dates the modern Treg and Tr1 work. TGFbeta can have effects on B cells, namely stimulating class-switching to IgG3, but is now generally regarded as a Treg cytokine, with mainly immunosupressive effects in blocking T cell proliferation, cytokine production and differentiation to Th1 and Th2 (see http://www.nature.com/nri/journal/v7/n6/full/nri2095.html). I'm not sure if any of the TGFbetaRII dominant-negative mice have Th2 defects though - might be worth looking that up. Kantokano (talk) 17:51, 5 March 2008 (UTC)

Thanks for the update and link to that excellent reveiw of PMID: 15280416. The IgG3 info is interesting given CFS has high TGF-b and low IgG 1 and 3 Also seems role in limiting autoimmunity of similar relevance, now only have to wait for trial! Can I suggest a new form of referencing for this page. Regards Jagra (talk) 04:33, 6 March 2008 (UTC)

references

Mosmann TR, Coffman RL. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annual Review of Immunology 1989, 7:145-173

Clerici M, Shearer GM. A TH1-->TH2 switch is a critical step in the etiology of HIV infection. Immunology Today, 1993 14(3) :107-111.

Clerici M, Shearer GM. The Th1-Th2 hypothesis of HIV infection: new insights. Immunology Today, 1994 Dec; 15(2) :575-81.

Lucey DR, Clerici M et al. Type1 and Type2 cytokine dysregulation in human infections, neoplastic and inflammatory diseases. Clin Microbiol Rev 9 (4) 1996: 532-562.

Peterson JD, Herzenberg LA, Vasquez K, Waltenbaugh C. Glutathione levels in antigen-presenting cells modulate Th1 versus Th2 response patterns. Proc Nat Acad Sci USA 1998; 95:3071-3076.

Murata, Y et al. The polarization of Th1/Th2 balance is dependent on the intracellular thiol redox status of macrophages due to the distinctive cytokine production. International Immunology 2002, 14(2): 201-212.

Mosmann TR. Cytokine patterns during the progression to AIDS. Science, 1994 Jul 8;265(5169):193-4.

Kidd P. Th1/Th2 balance: the hypothesis, its limitations, and implications for health and disease. Alternative Medicine Review, Aug. 2003. —Preceding unsigned comment added by 68.122.71.67 (talk) 21:43, August 27, 2007 (UTC)

The above are all great references, I would also include:

Janeway, Charles A. Immunobiology : the immune system in health and disease. 6th ed. New York : Garland Science, 2005.

Why aren't any of these included in the article?--Jkuruppu (talk) 16:50, 12 May 2008 (UTC)

Quite frankly, they're 1) largely out-of-date 2) overly specific to HIV infection, and more appropriate for that page. Similarly, while Janeway is a cornerstone of immunology education, there's already been a more recent edition by the time you added your article, and a new edition roughly every other year. Jbarin (talk) 10:21, 27 October 2010 (UTC)

B cell costimulation

Is there a particular reason CD40 and CD154 or CD40L were not mentioned in the article? The latter, apart from other cells is expressed by activated T cells and is important in costimulation of B cells through direct cellular contact.

Moreover, the section heading is "Stimulation of Naive T cells"; is the activation of memory T cells fundamentally different? I don't have much idea of this topic, hence the query.

Hope my doubts are answered. Thanks in advance.

Regards.

—KetanPanchal^taLK 12:25, 28 May 2008 (UTC)

CD40/CD154 signaling is only one of many costimulatory circuits used in T cell communication with B cells, dendritic cells, macrophages and other APC types. Its original characterization largely described unidirectional signaling (help for B cells), similar to the characterization of the B7 family. While these particular pathways are important, redundancy and non-redundancy among the many TNF superfamily members (which CD40/CD154 belong to), as well as the B7s makes the story frankly too fundamentally complex to discuss on a single page; I would recommend a completely separate discussion of costimulatory pathways as warranting its own page, if you're up to the task. Jbarin (talk) 10:26, 27 October 2010 (UTC)

"also known as effector T cells.."

I'm not sure the above is really correct. Certainly T helper cells are effector cells, but so are cytotoxic T cells. I think the AKA needs to be removed and reference made elsewhere that Th cells are amongst the effector (as opposed to memory) T cells. Thoughts? DoktorDec (talk) 02:51, 23 December 2008 (UTC)

TH22

New subtype, generating IL22, named T_h22 involved in psoriasis.[1] Rod57 (talk) 13:58, 26 September 2010 (UTC)

The new subpopulations of CD4+ cells in recent years, following the Th17 story, is getting well-beyond the ability of this page to keep up. I would probably simply append them to the brief discussion of Th9 cells, and probably add Tfh cells. Frankly, these stories, while exciting, haven't been robustly verified enough by independent investigators to be widely accepted in consensus just yet; perhaps in a few years. Jbarin (talk) 10:29, 27 October 2010 (UTC)

Subscript?

I checked out a few research papers and found NONE that has the h as subscript. Is there a reference to justify this? CielProfond (talk) 19:02, 27 November 2013 (UTC)

Express

Hey guys, "express" in the second paragraph, does it mean like "bind"? The text: Mature Th cells express the surface protein CD4 and are referred to as CD4+ T cells. CyberTroopers (talk) 11:30, 8 October 2020 (UTC)

It means that the Th cells make the surface protein CD4. It does not mean "bind." CatPath ^{meow at me} 12:03, 8 October 2020 (UTC)