Cytokine/chemokine cascades in immunity to tuberculosis

doi:10.1016/S0167-5699(98)01438-8

Immunology Today

Volume 20, Issue 7, 1 July 1999, Pages 307-312

Immunology Today

https://doi.org/10.1016/S0167-5699(98)01438-8 Get rights and content

Abstract

The relationship between acquired specific resistance and delayed-type hypersensitivity (DTH) in immunity to tuberculosis has long been a topic of debate. Here, Ian Orme and Andrea Cooper propose that the events are separate mechanisms; protection is cytokine driven and initially controls the infection, whereas DTH is primarily chemokine driven and functions to wall off the infection and prevent further dissemination.

Section snippets

The basis of immunity to tuberculosis

Since the observations by North that mice lacking T cells were highly susceptible to tuberculosis infection2, 3, and that of Lefford that T cells could transfer immunity4, 5, 6, the field has gradually (but slowly) advanced in terms of identifying the role of various T-cell subsets.

CD4⁺ T cells capable of transferring immunity appear rapidly after infection of mice⁷, and these cells secrete interferon γ (IFN-γ) after in vitro restimulation with filtrate antigens of Mycoplasma tuberculosis8, 9,

Early events in the lungs: a putative model

The hypothesis proposed is that infection is established in the lungs by the erosion of a bacterium into the interstitium, causing subsequent inflammation. The resultant immunity is triggered either by bacilli passing into the adjacent capillary, and hence into the vascular circulation, or via carriage by macrophages into the bronchial-associated lymphatic tissue (BALT) from the bronchial surface (the mouse alveolar region has little or no lymphatic drainage).

The model in Fig. 1 shows how an

Cytokine-driven protection and chemokine-driven DTH

In the mouse model, the protective response (IL-2, IL-12, IFN-γ) precedes the emergence of the lung chemokine response⁴⁷. So how are these mechanisms inter-related?

We would like to propose that protection and DTH are not only two separate mechanisms, but that they can be further distinguished by their preferential use of cytokines or chemokines as mediator molecules (Fig. 3). Protective immunity, as we view it, is an attempt by the host to prevent further spread of the infection by identifying

Conclusions

We have proposed as a working hypothesis, and of course as a stimulus for debate, the concept that ‘protective immunity’ and ‘DTH’ are two separate components of cell-mediated immunity to intracellular bacterial pathogens. If correct, the model has multiple implications for better vaccine strategies, which should target the cytokine-driven protective response (and subsequent memory T-cell generation), and improvements in skin test diagnostic reagents, in which the DTH response may not be

Acknowledgements

We thank our MRL colleagues E. Rhoades, B. Saunders, C. D'Souza and A. Frank for their contributions to the hypotheses stated above. This work was supported by NIH programs AI-40488, AI-41922 and AG-06946.

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ViewpointCytokine/chemokine cascades in immunity to tuberculosis

Abstract

Section snippets

The basis of immunity to tuberculosis

Early events in the lungs: a putative model

Cytokine-driven protection and chemokine-driven DTH

Conclusions

Acknowledgements

Cell. Immunol.

Immunol. Today

Curr. Opin. Immunol.

Curr. Opin. Immunol.

Curr. Opin. Immunol.

Curr. Opin. Immunol.

Curr. Opin. Immunol.

Tuber. Lung. Dis.

Res. Immunol.

Cell

Immunity

Res. Immunol.

J. Infect. Dis.

Infect. Immun.

Immunology

Infect. Immun.

Am. Rev. Respir. Dis.

J. Immunol.

J. Immunol.

J. Immunol.

Scand. J. Immunol.

Infect. Immun.

J. Immunol.

J. Immunol.

Proc. Natl. Acad. Sci. U. S. A.

J. Immunol.

Infect. Immun.

Infect. Immun.

Viewpoint
Cytokine/chemokine cascades in immunity to tuberculosis