TH1/TH2 cytokines

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TH1/TH2 cytokines

The term TH1 cytokines ( referred to also as Type-1 cytokines ) and TH2

cytokines ( referred to also as Type-2 cytokines ) refers to the patterns of

cytokines secreted by two different subpopulations of murine CD4 (+)T-cells

(see also: CD antigens ) that determine the outcome of an antigenic response

toward humoral or cell-mediated immunity.

Numerous cells other than T-cells expressing CD4 have been shown to be

capable of producing TH1 cytokines and TH2 cytokines . These cells include

CD8 (+)T-cells, monocytes, natural killer cells, B-cells, eosinophils, mast

cells, basophils, and other cells. Type-1 cytokines include IL2 , IFN-gamma

, IL12 and TNF-beta , while Type-2 cytokines include IL4 , IL5 , IL6 , IL10

, and IL13 .

Type-1 helper cells (TH1), but not type-2 helper cells (TH2), secrete IL2 ,

IFN-gamma , and TNF-beta , whereas TH2 cells, but not TH1 cells, express IL4

, IL5 , IL6 , and IL10 . Murine TH2 cells, but not TH1 cells, also express

P600 , the human counterpart of which has been identified as IL13 . A novel

cytokine inducing the synthesis of IFN-gamma in TH1 cells has been

identified recently as IGIF (and renamed IL18 (see also: Interleukins )).

The molecular mechanisms underlying the evolution of these two different

cell types from common precursors are still not completely known. Studies

with transgenic mice carrying null mutations of the IL4 gene (see also:

Knock-out ) have shown that IL4 plays an important role in the establishment

of a functional TH2 immune response.

The different patterns of cytokine secretion correspond with different

functions as immune effectors. TH1 cells promote cell-mediated effector

responses. TH2 cells are mainly helper cells that influence B-cell

development and augment humoral responses such as the secretion of

antibodies, predominantly of IgE, by B-cells. Both types of TH cells

influence each other by the Cytokines they secrete; IFN-gamma , for example,

can downregulate TH2 clones while TH2 cytokines , such as IL10 (see also:

CSIF , cytokine synthesis inhibitory factor ), can suppress TH1 functions.

IFN-gamma has been shown also to inhibit the proliferation of murine TH2

cells but not that of TH1 helper T-lymphocyte clones. It thus appears that

these functional subsets are mutually antagonistic such that the decision of

which subset predominates within an infection may determine also its

outcome.

Murine IL12 has been shown recently to alter differentiation of a subset of

CD4 (+)cells and to be involved in the induction of protective immunity

against intracellular parasitic infections in mice. IL12 appears to prevent

deleterious TH2 T-cell responses and to promote curative TH1 responses in an

IFN-gamma dependent fashion during murine leishmaniasis. Another exogenous

factor also influencing the development of undifferentiated CD4 (+)T-cells

towards either the TH1 or TH2 phenotype is TGF-beta .

A third subset of memory cells, designated TH0 cells and believed to be

precursor cells that develop into either TH1 or TH2 cells, can produce all

Cytokines found to be secreted either by TH1 or TH2 cells at low levels.

It appears that different types of helper cell populations resembling those

observed in mice are found also in humans. However, the differences in

cytokine expression seems to be quantitative rather than qualitative.

References: Bloom BR et al Revisiting and revising T suppressor cells

Immunology Today 13: 131-6 (1992); Bottomly K A functional dichotomy in CD4

+ T lymphocytes Immunology Today 9: 268-74 (1988); Cherwinski HM et al Two

types of mouse helper T cell clone. III. Further differences in lymphokine

synthesis between Th1 and Th2 clones revealed by RNA hybridization,

functionally monospecific bioassays, and monoclonal antibodies. Journal of

Experimental Medicine 166: 1229-44 (1987); Clerici M and Shearer GM A TH1 to

TH2 switch is a critical step in the etiology of HIV infections Immunology

Today 14: 107-111 (1993); del Prete GF et al Purified protein derivative of

Mycobacterium tuberculosis and excretory-secretory antigen(s) of Toxocara

canis expand in vitro human T cells with stable and opposite (type 1 T

helper or type 2 T helper) profile of cytokine production. Journal of

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TH2 CD4 + clones exist? Research Immunology 142: 59-63 (1991); Fiorentino DF

et al IL10 acts on the antigen-presenting cell to inhibit cytokine

production by Th1 cells. Journal of Immunology 146: 3444-51 (1991);

Firestein GS et al A new murine CD4 + T cell subset with an unrestricted

cytokine profile. Journal of Immunology 143: 518-25 (1989); Gajewski TF and

Fitch FW Anti-proliferative effect of IFN-gamma in immune regulation. I.

IFN-gamma inhibits the proliferation of Th2 but not Th1 murine helper T

lymphocyte clones. Journal of Immunology 140: 4245-52 (1988); Heinzel FP et

al Recombinant interleukin 12 cures mice infected with Leishmania major.

Journal of Experimental Medicine 177: 1505-9 (1993); Hikida M et al

Suppression of interleukin 4 production from type 2 helper T cell clone by

antisense oligodeoxynucleotide. Immunology Letters 34: 297-302 (1992);

Kamogawa Y et al The relationship of IL4 and IFN-gamma-producing T cells

studied by lineage ablation of IL4 producing cells. Cell 75: 985-95 (1993);

Kapsenberg ML et al Functional subsets of allergen-reactive human CD4 + T

cells Immunology Today 12: 392-5 (1992); Kawakami K and DC

Differences between T helper cell type I (Th1) and Th2 cell lines in

signaling pathways for induction of contact-dependent T cell help. European

Journal of Immunology 22: 85-93 (1992); Kelso A et al Heterogeneity in

lymphokine profiles of CD4 + and CD8 + T cells and clones activated in vivo

and in vitro. Immunological Reviews 123: 85-114 (1991); Lederer JA et al

Regulation of cytokine gene expression in T helper cell subsets. Journal of

Immunology 152: 77-86 (1994); Maggi E et al Reduced production of

interleukin 2 and interferon-gamma and enhanced helper activity for IgG

synthesis by cloned CD4 + T cells from patients with AIDS. European Journal

of Immunology 17: 1685-90 (1987); Mosmann TR et al Two types of murine

helper T cell clone. I. Definition according to profiles of lymphokine

activities and secreted proteins. Journal of Immunology 136: 2348-57 (1986);

Mosmann TR and Coffman RL Heterogeneity of cytokine secretion patterns and

functions of helper T cells. Advances in Immunology 111-47 (1989); Mosmann

TR and Coffman RL TH1 and TH2 cells: different patterns of lymphokine

secretion lead to different functional properties. Annual Review of

Immunology 7: 145-73 (1989); WE and Seder RA Lymphocyte responses and

cytokines. Cell 76: 241-51 (1994); Rocken M et al A common precursor for CD4

+ T cells producing IL2 or IL4. Journal of Immunology 148: 1031-6 (1992);

Romagnani S Type 1 T helper and type 2 T helper cells: functions, regulation

and role in protection and disease. International Journal of Clin. Lab.

Research 21: 152-8 (1991); Romagnani S Human TH1 and TH2 subsets: doubt no

more Immunology Today 12: 256-7 (1991); Rooney JW et al A common factor

regulates both Th1- and Th2-specfic cytokine gene expression EMBO Journal

13: 625-33 (1994); Trinchieri G et al Interleukin-12 and its role in the

generation of TH1 cells Immunology Today 14: 335-8 (1993); Vowels BR et al

Aberrant cytokine production by Sezary syndrome patients: cytokine secretion

pattern resembles murine Th2 cells. Journal of Investigative Dermatology 99:

90-4 (1992); ME et al Activation of functionally distinct subsets

of CD4 + T lymphocytes. Research Immunology 142: 23-8 (1991)

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