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Table of Content
S.No Contents Page No.
1 General introduction to immune system and helper T cells 3
2 What are cytokines 4
3 Functions of helper T cells in immune system 6
4 Interaction of different helper T cell with other immune system cells 10
5 Production of cytokines from helper T cells 11
6 Action of helper T cells cytokines on other immune system cells 12
7 Production of cytokines from other cells and their action on helper T cells 13
8 Function of cytokines from other cells in induction of helper T cells 14
9 Biological effects of helper T cells 16
10 References 18

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1. General introduction to immune systemand helper T cells
Immune system
The term immunity is derived from Latin word which refers to the general ability of the
host body that resist the particular infection or disease is called immunity or immune systems
which are composed of immune cells, tissues and organ that recognized the foreign substances
like microbes. When we study each immune system in detail including their types structure and
function etc is called immunology that is the branch of medical science.
There are two broad types of immune system that are activated against invading
microorganisms’ i.e. innate immune system and adaptive immune system. The innate immune
systems are activated against every kind of microbes within a minute or second that are found in
vertebrate host. It acts as 1st line of defense system that includes skin, mucus and lysozymes. On
the other hand the adaptive immune system is activated against particular microbes within an
hour or days to week that are also found in vertebrate host when the innate immunity lost their
recognition. It has immunological memory that are absent in innate immunity.
The substances that activate or provokes the immunity is called antigen That cause the B
cells to replicate, make and produces antibody that binds to antigens and eliminate the microbes
by destroying each microbes thus protect the host body. In both immune system there are
immune cells involves called as WBCs or leucocytes that are developed in bone marrow by stem
cells through a process called as hematopoesis. Each immune cell involves neutrophils,
monocytes (macrophages and dendritic cells), lymphocytes (B & T lymphocytes), mast cells,
eosinophils and basophiles.

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Helper T cells
The T helper cells are also called as CD4+ cells which are a type of T cell that play a
significant role in immunity mainly in the adaptive immunity. They help to regulate the other
immune cells by releasing of T cell cytokines . These cells are also involved in suppression or
regulation of immune responses in the body. The helper T cells are activated through antigen
presented by the class of MHC II molecules that is found on APCs.
2. What are cytokines
The term cytokines are derived from Greek words which mean cell movement. The
cytokines are any soluble proteins that are secreted by one cell population and acts as an
intercellular i.e. between cells mediator and signaling molecule. When it is released from
mononuclear phagocytes then these proteins are known as monokines, when these proteins are
produced from T lymphocytes then they are known as lymphokines, when these proteins are
released by a leukocyte and their functions act on another leukocyte then they are called as
interleukins and if their result is to regulate the growth and differentiation of immature
leukocytes in the bone marrow then they are called colony-stimulating factors (CSFs). Cytokines

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have been grouped into the following categories or families i.e. chemokines, hematopoietins,
interleukins, and members of the tumor necrosis factor (TNF) family.
When the cytokines affect the same cell responsible for their production then it is called
as autocrine function or nearby cells then it is paracrine function or they can be spread by the
circulatory system to far target cells then it is an endocrine function. Their production is changed
or stimulated by nonspecific stimuli such as a viral, bacterial or parasitic infection; cancer;
inflammation or the communication between a T cell and antigen. Some cytokines also induce
the production of other cytokines. Most cells have many cytokine receptors, but the function mat
be done when it is occupied by each cytokines. This binding activates specific intracellular
signaling pathways that switch on genes encoding proteins essential to the suitable target cell
functions. For example, cytokine binding may result in the target cell’s production of other
cytokines, cell-to-cell adhesion receptors, proteases, lipid-synthesizing enzymes and nitric oxide
synthase. In addition, cytokines can stimulate cell proliferation, cell differentiation, cell division
and apoptosis. Interferon (IFNs) are a group of related low molecular weight, regulatory
cytokines produced by certain eukaryotic cells against to a viral infection and also help to
regulate the immune response.

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3. Functions of helper T cells in immune system
There are three types of helper T cells i.e. TH0 cells, TH1 cells, and TH2 cells. TH0 icells
iare isimply iundifferentiated iprecursors iof iTH1 icells iand iTH2 icells, iwhile iTH1 iand iTH2 icells iare
idistinguished iby ithe idifferent itypes iof icytokines ithey iproduce. iThe iTH0 iare iprecursor icells ithat
iare iactivated iby ispecific iantigen ipresented ion iclass iII iMHC ito idifferentiate iinto iTH1 ior iTH2 icells.
iActivated iTH1 icells ipromote icytotoxic iT ilymphocyte i(CTL) iactivity, iactivate imacrophages, iand
imediate iinflammation iby iproducing iinterleukin i(IL)-2, iinterferon i(IFN), iand itumor inecrosis
ifactor i(TNF). iThese icytokines iare ialso iresponsible ifor idelayed-type i(type iIV) ihypersensitivity
ireactions, iin iwhich ihost icells iand itissues iare idamaged inonspecifically iby iactivated iT icells. iTH2
icells itend ito istimulate iantibody iresponses iin igeneral, iand idefend iagainst ihelminthes iparasites iby
iproducing icytokines isuch ias iIL-4, iIL-5, iIL-6, iIL-10, iand iIL-13. iAniexcess iofiTH2 itype iresponses
imay ialso ibeiinvolved iin ipromoting iallergic ireactions.
 Activation of macrophages at infection sites
The TH1 are induced by APCs that recognized microorganisms in vesicles. When the
dendritic and macrophages cells are infected then each cells accumulate the helper T cells to kill
such microbes. The dendritic cells travel to peripheral lymphoid organs and stimulate the TH1
cells productions which then transfer to the infectious site to stimulate macrophages to kill the
microbes which are recognized in their phagosomes. The TH1 activate the macrophages by using
2 signals. They produce IFN-γ, which binds to IFN-γ receptors on macrophage surface, and they
display the costimulatory protein CD40 ligand, which binds to CD40 on the macrophage. Once
the macrophages activated then they kill the microbes by phagolysosomes activity. On the other
hand the dendritic cells also express the CD40 on their surface thus TH1 also activate these cells
at infectious sites. Thus the dendritic cells enhance their secretion of class II MHC proteins, B7
costimulatory proteins, and various cytokines, especially IL-12 due to which it is more effective
at regulating helper T cells to differentiate into TH1 cell in peripheral lymphoid organs and then
activate macrophages.
The TH1 cells regulate an inflammatory response to accumulate more phagocytic cells into
infected site by the three following way:

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1. They produce cytokines that act on the bone marrow to enhance the monocytes and
neutrophils secretion.
2. They release other cytokines that stimulate endothelial cells that accumulate monocytes
and neutrophils in the blood.
3. They secrete chemokines to migrate the neutrophils and monocytes to infectious site.
The TH1 cells also activate cytotoxic T cells in peripheral lymphoid organs to stimulate
dendritic cells that secrete more co-stimulatory proteins that help the cytotoxic T cell to kill virus
infected cells. The TH1 cells can also directly kill some cells by itself because they also including
effector lymphocytes that expressing Fas ligand on its surface. Both TH1 and TH2 cells can
activate B cells which are changed into either plasma cells or memory cells. They can also
regulate B cells that activate antibody like IgM and IgD.

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 Role in disease controlling
As helper T cells can perform their in immune system so it controls different kind of
disease because of immune system activation against different disease.
A. Hypersensitivity
The hypersensitivity that cause allergy and some of autoimmune disease are also
controlled by each helper T cell. The type 1 hypersensitivity that cause asthma, hay fever, hives
and anaphylaxis. The THC2 will suppress each mast cell that causes each disease. The THC2 are
also involved in Type 2 & 3 hypersensitivities reaction that cause low affinity antibodies. Now
the THC2 will secrete cytokines that will ultimately activate the B cells and produces auto-
specific antibodies to eliminate the disorder of low affinity antibodies. Now the hypersensitivity
type 4 that cause the overregulation of macrophages and lymphocytes that leads to chronic
inflammation. The THC1 release different kind of cytokines that will activate and promote the
macrophages to control the overregulation of macrophages and lymphocytes. Other cellular
hypersensitivities i.e. Cytotoxic T cell that activate auto-immune disease and a phenomenon
called as transplant rejection. Helper T cells will create enough auto-reactive killer T
cells, interleukin-2 must be formed and this is supplied by CD4+ T cells that also stimulate
natural killer cells and macrophages by interferon-gamma cytokines that encourages these
cytotoxic cells to kill host cells in definite situation.

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B. COVID-19
COVID-19 caused by the SARS CoV2 which is the third major lower respiratory tract
corona virus infection in the 21st century, after SARS and MERS. Therefore, several
immunotherapies that target various inflammatory processes have been successfully used in
COVID-19 patients new research has been conducted on th-17 for controlling of COVID-19
because it can release the cytokines i.e. IL-17 and GM-CSF. The Th 17 can also produce IL-6
which may help to activate the neutrophils and eosinophils against each SARs COV-2.
C. HIV infections
As the HIV infect the CD4 T cell which activate the Helper T cells but during non-
symptomatic phase the viruses will kill low number of CD4 cells. Soon after that more new
Helper T cells are produced and mature in the thymus and eventually they activate the other
immune cells like macrophages and neutrophils against each virus. Thus the infections are under
the control and the diseases are eliminated.
D. Tumor cells destruction and cancer controlling
The helper T cells secrete the TNFs cytokines that will activate the natural killer and
cytotoxic T cells against the tumor cells to control and prevent each cell from cancer disease
causing by the destruction of each cells. This cytotoxic T cell will bind ultimately on tumor cells
and then release the perforine and granzymes to kill that cell.
 Memory T cell preparation
During new infection the helper T cells are involves to control each infection for the first
time and take a long time to control each new infective disease during which the body will
tolerate more harm. So for that the T helper cells will form the memory T cells to prevent such
long time against each new infective disease. Thus during 2nd of the same infective disease the
memory T cell will already prepared and will kill rapidly each disease as compare to the 1st
infection case. It is just like memory B cells.

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4. Interaction of different helper T cell with other immune system cells
There different helper T cells that are involve in the interaction with other immune cells.
During infection when the antigen or microbes are engulfed by antigen presenting cells (APCs)
like macrophages and dendritic cells then they will secrete different cytokines due to which
different helper T cells are interacted like cytotoxic T lymphocytes, HTC1 and HTC2. First the
helper T cell will interact with the APCs and after interaction the helper T cells will get activated
and then interact with B cell to activate it. Now the B cell will differentiate in to plasma cells that
secrete antibody against each microbes or antigen that are engulfed by APCs. Some time the
antibody will kill each microbe alone and some time it will convey massage to other APCs to kill
each microbe. If the Antigen presenting cells are infected by viruses then they will activate the
cytotoxic T lymphocytes or HTC1 that will ultimately kill the virus infected cell.
On the other hand if tumor cells are generated that cause cancer then natural T killer cells
are activated to kill the tumor cells. Sometimes a lot of APCs, Granulocytes and other immune
cells are activating due to which hyper immune cell activation occur and cause autoimmune
disease. There are T reg cells involved that release different kinds of cytokines to control hyper
immune cell activation.

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5. Production of cytokines from helper T cells
In 1986, Mosmann and Coffman discovered 2 subsets of activated CD4 T cells, Th1 and
Th2 cells in 1986 that are different according to cytokines production and their function. There
are almost important 4 CD4 T-cell i.e. Th1, Th2, Th17, and Treg cells that released different
cytokines and thus help in immune system to eliminate the disease. They play important role in
adaptive immunity to different microorganisms. They are different by their unique cytokine
production and their functions like Th1 cells mainly generate interferon-γ (IFNγ) and are
important and express immune responses against intracellular viral and bacterial infection, the
Th2 cells that produce interleukin-4 (IL-4), IL-5, IL-9, IL-13, and IL-25, that are responsible to
eliminate extracellular parasites such as helminthes, the Th17 that secrete IL-17a, IL-17f, and IL-
22 that are responsible for controlling or eliminating extracellular bacteria and fungi.
The organization of an immune response is dependent on the aptitude of CD4 T cells to
do a unique set of effectors functions. Along with these effectors functions is the capacity of
CD4 T cells to produce a unique cytokines i.e. IL-2, IL-4, and IFN-γ. Although most antigen-
specific CD4 T cells have the probable to produce all of these cytokines, CD4 T cells uncovered
to specific microenvironments can distinguish into two termed i.e. TH1 and TH2 cells. These
two subsets are controlled cytokines that they can generate. Thus TH1 cells produce IL-2 and
IFN-γ, while TH2 cells produce IL-4 as well as IL-5, IL-6, IL-10, and IL-13.

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6. Action of helper T cells cytokines on other immune systemcells
As there are many helper T cells are involves in immune system like ThC1, ThC2
ThC17, Follicular ThC and T reg C. These kind of helper T cells will released different cytokines
and each cytokines have different function on other immune cells. For examples:
 The ThC1 release IL-2 that performs their action against intracellular viral and bacterial
infection. They Stimulates, proliferation and differentiation T-cells; Enhances cytolytic
activity of NK cells; promotes proliferation and Ab secretion of activated B cells. It also
produce IFN- gamma that will perform Activation of T cells, macrophages, neutrophils,
and NK cells; increases class I and II MHC molecule expression on various cells
 The ThC2 secrete IL-4, that differentiate the B cells into Plasma cells to secrete antibody
against microbes, IL-5 that provide growth and activation to B cells and eosinophils due
to which eosinophils perform chemotactic process, IL-10 that Reduces the production of
IFN-, IL-1, TNF-, and IL-6 by macrophages; in combination with IL-3 and IL-4, causes
mast cell growth; in combination with IL-2, causes growth of cytotoxic T cells and
differentiation of CD8+ cells.
 The HTC 17 secretes IL-17 and IL-22 during fungal or bacterial infection. During
infection when APC secrete IL-6 and TGF- beta then nive T cell will converted in helper
T cell 17 that secrete IL-17 and IL-22. The IL-17 activates the neutrophils and recruits it
at infection sites. On the other hand IL-22 stimulates epithelial cells to secrete
antimicrobial peptides against microbes.
 The Follicular ThC secretes IL-21 that guides the B cells to make appropriate Ab against
the microbial infection.
 During hyper immune cell activation that cause autoimmune disease the T reg cells will
get activated that secrete IL-10 and TGF-beta. The IL-10 will suppress the Macrophages
activation and the TGF-beta will induce the production of more T reg cells. Finally the
immune system will be suppressed during that hyper immune cell activation by T reg
cells.
 The cytotoxic T lymphocytes will be activated when the cell is infected with viruses. The
cytotoxic T cell interact with infected cells and when proper interaction occur between
each cells via receptor then the cytotoxic T cell will secrete granzymes and perforine that
will ultimately kill the infected cell by pores formation in these infected cells.

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7. Production of cytokines from other cells and their action on helper T cells
The helper T cell can perform their function whenever it will bind to other cytokines
produced by other cell of the body. For the helper T cell activation the APCs will secrete 2
signal in which 1st signal is provide by the MHC protein when it is bounded with fragment of
antigens then through this signal the helper T cell will activated and bind with this MHC
molecules. The 2nd signal is provided by B7 protein and interact the helper T cell.
The two important cytokines like IL-12 and IFN that are responsible for Th1 differentiation.
The cytokines like IL-4, IL-2, IL-7 and thymic stromal lymphopoietin (TSLP) may be involved
in the differentiation of th2. While promoting growth factor-β (TGFβ) change Th17
differentiation in the presence of IL-6, which transfer iTreg cell differentiation when IL-2 are
available.
When the APCs engulfed the foreign particles then they will secrete IL-12 that differentiate
the naive T cells into ThC-1that will activate Macrophages and other T cell. There are also IL-2
that are secreted by somatic cells when it is infected and due to this IL-2 they will activate the
cytotoxic T lymphocytes and kill that infected cell by the release of perforine and granzymes.

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The macrophage secretes IL-4 and activates ThC-2 and that ThC-2 will activate B cell to
produce Ab against pathogen. The dendritic that secretes IL-6 and TGF-beta that will activate
helper T cell to recruits neutrophils at infection sites and also antimicrobial peptide against
microbes. The epithelial cells release chemoattractant like macroglobulin that will interact the
immature T helper cell in the thymus to mature and train the helper T cells for the infectious
particles or substances.
8. Function of cytokines from other cells in induction of helper T cells
There iare idifferent inumbers iof icytokines iproduce iby idifferent icells ithat iare irequired ifor
ihelper iT icell iinduction. iOne iof ithe ireports isays ithat iT ihelper iresponse iat imucosal isurfaces
idemonstrates iTh2 idivision, iwhich iis ireflected iin ithe icytokine iprofiles iof iactivated iT icells ifrom
imucosal ilymph inodes. iThis istudy ion irat irespiratory itract iDCs i(RTDCs) iprovides ian iexplanation
ifor ithis iparadox. iHowever, ipreculture iwith igranulocyte/macrophage icolony istimulating ifactor
iincreased ithe iin ivivo iIgG ipriming icapacity ithat imay iinduce iproduction iof iboth iTh1- iand iTh2-
dependent iIgG isubclasses iand ihigh ilevels iofiIFN-gibyiantigen-stimulated isplenocytes. I

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Several iimmune ireactions isuch ias iT-B icollaboration iand ithe ikilling iof ivirus-infected icells
ihave ibeen ishown ito ibe ilinked ito ithe iH-2 iregion iof ithe imajor ihistocompatibility ilocus. iThe iresults
ishowed ithat ithe iinability iof iallogeneic imacrophages ito iparticipate iin ihelper icell iinduction iwith
isoluble iantigens iwas inot idue ito ithe ipresence iof isuppressor icells igenerated iin ithese icultures ibut
iwas idue ito ia igenetic irestriction iof ithe imacrophage-T-cell iinteraction iwhich iwas igoverned iby ithe
iI-A iregion iof ithe iH-2 icomplex. iHelper icell iinduction ito inon iparticulate iantigens iin ivitro irequires
ithe icooperation iof iT icells iand imacrophages, ibut idoes inot ioccur iif ithe imacrophages iare iallergenic.
iThe ireasons ifor ithis iwereiinvestigated. I
As iwe iknow ithat iautoimmunity iis ithought ito ireflect ian iimbalance ibetween iTreg icells iand
ipathogenic, iIL-17-secreting iT ihelper i(Th17) icells. iInduction iof iboth iadaptive iTreg iand iTh17 icells
irequires isignalling ifrom iTGF-b. iWe inow ishow ithat, iin ithe icontext iof iTGF-b isignalling, iall-trans
iretinoic iacid i(ATRA) ileads ito iincreased iinduction iof iCD4+ iT icells iexpressing ithe iTreg
ispecification ifactor iforkhead ibox iprotein iP3 i(FoxP3) iand idecreased ifrequency iof icells iexpressing
iIL-17, ieven iin ithe ipresence iof iIL-6. iUsing ia ispecific iagonist iand iantagonist, ias iwell ias iretroviral
iover-expression, iwe ialso iprovide ievidence ithat ithe ieffects iof iATRA iare ilikely ito ibe iat ileast
ipartially imediated iby ithe inuclear iretinoic iacid ireceptor-a i(RARa). iThese ifindings iindicate ithat
isignalling ithrough ia ispecific inuclear iretinoic iacid ireceptor ican ifavour ithe idecision ito iadopt ithe
iTreg ifate iat ithe iexpense iof iTh17 ifate. iSpecific iagonists iof iRARa icould, itherefore, ibe iconsidered
icandidates ifor ithe itreatment iofiautoimmunity.
Thus from the above discussion we can say that if the APCs are recognized by helper
Treg cell and then the APC cell will secrete proinflamatory cytokines. This will cause the
production of large number of other T cells and immune cell component. Thus hyper immune
cell regulation will occur. The Treg cell during interaction with APC secrete IL10 and effect on
APCs due to which it will not produce any more IL-6, IL1 and TNF alpha. The IL-2 will be
secreted from Treg cells that will activate helper T cell and other Treg cell. Moreover the Treg
cells will secrete IL-10 and TGF-beta due to which more and more immune cells will be
suppressed and cell destruction pathway is activated due to which the helper t cell are die and the
hyper immune cell regulation will be controlled.

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9. Biological effects of helper T cells
Proinflammatory icytokines i(e.g., iIL-1β, iTNF-α) iand ichemokines i(e.g., iMCP-1) imay
idirectly ialter ineuronal iaction iin ivarious iclasses iof ineurons iin ithe iperipheral iand icentral inervous
isystem. iIt iwas ifound ithat iTNF-α-induced ineuronal iexcitation iis imediated iby icAMP-dependent
iprotein ikinase i(PKA) ipathway. iThe ip38 imitogen-activated iprotein ikinase i(MAPK) iis ialso
iinvolved iin iTNF-α- iinduced icutaneous ihypersensitivity itoimechanical iorithermal istimulation.
The Results iobtained ifrom iIL-6 iknockout imice iindicate ithat iIL-6 iplays ia ifacilitating irole
iin isympathetic isprouting iinduced iby inerve iinjury iand ithat iits ieffect ion ipain ibehavior iis iindirectly
imediated ithrough isympathetic isprouting iin ithe iDRG. iMost irecently, iit iis ireported ithat ilocalized
iinflammation iof ithe iDRG iup-regulates ia inumber iof iproinflammatory icytokines iincluding iIL-6
iand iinduces iabnormal iconcerned ideveloping iin ithe ilack iofiperipheral inerve iinjury
The numerous types of thymus epithelial cells play a significant role in development of T
helper cells by producing numerous thymus hormones like thymoprotein and thymosine with

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their several biological activities like they T cell differentiation and enhance the activity of
mature T cells. The T helper cell i.e. cytotoxic T lymphocytes are helpful in the controlling of
tumor cells that cause cancer. All these process is just done for the autoimmune disease
controlling which is actually a biological effect of helper T cells. Moreover the function of helper
T cells in immune system that we discussed in page No 6 we can also say that it is the biological
effects of helper T cells.

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