The Th1–Th2 hypothesis of HIV infection: new insights

doi:10.1016/0167-5699(94)90220-8

Immunology Today

Volume 15, Issue 12, December 1994, Pages 575-581

Immunology Today

https://doi.org/10.1016/0167-5699(94)90220-8 Get rights and content

Abstract

In their earlier, much quoted, viewpoint article, Mario Clerici and Gene Shearer examined the role of T helper 1 (Th1)- and Th2-type responses in immune dysregulation associated with human immunodeficiency virus (HIV) infection. In this article, they consider the complications of a Th1–Th2 model raised by the nomenclature, discuss the issue of cytokine production by non-T cells, and compare data obtained from T-cell clones with heterogeneous populations of leukocytes from patients. They define Th-cell responses and cytokine profiles as ‘type 1’ and ‘type 2’, and reemphasize the importance of strong cellular immune responses, along with the cytokines that augment and maintain such responses, in protective immunity against HIV infection and AIDS progression. Finally, they present a model of activation-induced, cytokine-modulated, programmed cell death as a major factor in the pathogenesis of HIV infection and AIDS.

References (104)

M. Clerici et al.
Immunol. Today
(1993)
S. Romagnani
Immunol. Today
(1991)
G. Zurawski et al.
Immunol. Today
(1994)
E. Legac et al.
Blood
(1992)
D. Antoniskis et al.
Am. J. Med.
(1990)
S.L. Rowland-Jones et al.
Lancet
(1993)
D.N. Wright et al.
J. Allergy Clin. Immunol.
(1990)
M.H. Grieco
J. Allergy Clin. Immunol.
(1989)
D. Israel-Biet et al.
J. Allergy Clin. Immunol.
(1992)
R.A. Kaslow et al.
Lancet
(1990)

P. Gladstone

Immunol. Today

(1993)

T. Takahashi et al.

Cell

(1994)

G. Le Gros et al.

Curr. Opin. Immunol.

(1994)

E.S. Browne et al.

J. Steroid. Biochem. Mol. Biol.

(1993)

G.A.W. Rook et al.

Immunol. Today

(1993)

G.A.W. Rook et al.

Immunol. Today

(1994)

M. Clerici et al.

J. Clin. Invest.

(1989)

M. Clerici et al.

J. Clin. Invest.

(1993)

M. Clerici et al.

J. Clin. Invest.

(1994)

M. Clerici et al.

J. Infect. Dis.

(1991)

M. Clerici et al.

J. Infect. Dis.

(1992)

M. Clerici et al.

AIDS

(1993)

M. Clerici et al.

J. Am. Med. Assoc.

(1994)

J. Cohen

Science

(1993)

T.R. Mosmann

Science

(1994)

E. Maggi et al.

Science

(1994)

J. Chehimi et al.

J. Exp. Med.

(1994)

J. Salk et al.

Science

(1993)

M. Yamamura et al.

Science

(1991)

L.J. Montaner et al.

J. Exp. Med.

(1993)

A. Zlotnik et al.

Cytokine

(1991)

J. Chehimi et al.

J. Clin. Immunol.

(1994)

P.L. Dunn et al.

Infect. Immun.

(1991)

Meyaard, L., Otto, S.A., De Jong, R. and Miedema, F. Blood (in...

A. Vyakarnam et al.

J.A. Levy

XI Int. Conf. AIDS

C.M. Walker et al.

Immunology

(1989)

G. Ferrari et al.

J. Cell. Biochem.

(1993)

W. Barcellini et al.

AIDS

(1994)

F. Ameglio et al.

J. Cell. Biochem.

(1993)

V. Navikas et al.

Clin. Exp. Immunol.

(1994)

E. Maggi et al.

J. Exp. Med.

(1994)

Denis, M. and Ghadirian, E. AIDS Res. Hum. Retrovir. (in...

Navikas, V., Link, J., Wharen, B. et al. AIDS Res. Hum. Retrovir. (in...

C. Graziosi et al.

Science

(1994)

P. Debré et al.

XI Int. Conf. AIDS

M. Clerici et al.

Science

(1993)

G.M. Shearer et al.

J. Clin. Invest.

(1985)

D.S. Ridley et al.

Int. J. Lepr.

(1966)

P.F. Barnes et al.

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viewpointThe Th1–Th2 hypothesis of HIV infection: new insights

Abstract

Immunol. Today

Immunol. Today

Immunol. Today

Blood

Am. J. Med.

Lancet

J. Allergy Clin. Immunol.

J. Allergy Clin. Immunol.

J. Allergy Clin. Immunol.

Lancet

Immunol. Today

Cell

Curr. Opin. Immunol.

J. Steroid. Biochem. Mol. Biol.

Immunol. Today

Immunol. Today

J. Clin. Invest.

J. Clin. Invest.

J. Clin. Invest.

J. Infect. Dis.

J. Infect. Dis.

AIDS

J. Am. Med. Assoc.

Science

Science

Science

J. Exp. Med.

Science

Science

J. Exp. Med.

Cytokine

J. Clin. Immunol.

Infect. Immun.

XI Int. Conf. AIDS

Immunology

J. Cell. Biochem.

AIDS

J. Cell. Biochem.

Clin. Exp. Immunol.

J. Exp. Med.

Science

XI Int. Conf. AIDS

Science

J. Clin. Invest.

Int. J. Lepr.

viewpoint
The Th1–Th2 hypothesis of HIV infection: new insights