chen_edit.qxp 12/5/08 12:42 pm Page 20
HIV and AIDS
Harnessing of Antigen-specific γδ T-cell Immune Responses
Against Mycobacterial Infections
a report by
Zheng W Chen, MD, PhD
Professor of Immunology and Microbiology, and Director, Center for Primate Biomedical Research, University of Illinois College of Medicine
AIDS and tuberculosis (TB) remain the two leading causes of mortality Human γδ T cells may contribute to immune responses to TB, although the
among infectious diseases.
1,2
While HIV increases susceptibility to TB, importance of these cells in immunity to TB has not been seen in mice.
24
Mycobacterium tuberculosis can enhance the pathogenicity of HIV.
3
However, it is important to know that mycobacterial antigens recognized
Emergence of the multidrug-resistant (MDR)/the extensively MDR (XDR) by mouse γδ T cells have not been defined, and the human γδ T-cell subset
M. tuberculosis has posed even greater threats to public health expressing T-cell receptors (TCRs) comprising Vγ2Vδ2 elements (Vγ2Vδ2
throughout the world.
4
Cell-mediated immune responses appear to play T cells) remains the only cell subpopulation that can recognize
a central role in immunity against TB or AIDS-related TB. It is therefore phosphoantigen produced by M. tuberculosis, bacillus Calmette-Guérin
important to explore cellular immune responses for harnessing (BCG), and other microbes.
24
Thus, the role of human antigen-specific
antimycobacterial immunity. This article overviews the recent progress for γδ T cells in immunity against TB remains to be characterized.
our understanding of antigen-specific γδ T-cell responses in mycobacterial
infections, and discusses the principle and potential of γδ T-cell-based
immune enhancement of antimicrobial cellular responses against TB- or Studies in humans have demonstrated
AIDS-related mycobacterial diseases.
that HIV-infected persons are susceptible
T-cell Populations and Antituberculosis Immunity to tuberculosis, suggesting that CD4
T-cell-mediated immunity plays a crucial role in protection against TB. T-cell
T cells are of central importance for
populations of CD4, CD8, and γδ T cells have been studied for their immune
responses or function in TB. It is likely that all T-cell populations contribute immunity to Mycobacterium
to immune responses to M. tuberculosis infection in humans, although it is
tuberculosis infection.
not known how these cells act in concert to develop immunity to TB. Data
generated in murine models indicate that CD4 T cells play a crucial role in
immune protection against TB.
5–10
Studies in humans have demonstrated Innate and Adaptive Features of Major γδ T-cell Subset in
that HIV-infected persons are susceptible to TB, suggesting that CD4 T cells Humans and Non-human Primates
are of central importance for immunity to M. tuberculosis infection.
11–13
Accumulating evidence suggests that human γδ T cells belong to non-
Recent studies in simian immunodeficiency virus of macaques (SIVmac)- classic T cells that contribute to both innate and adaptive immune
infected monkey models provide additional evidence that control of an responses. Resident γδ T cells within epithelia make up a portion of
active AIDS-virus-related mycobacterial disease requires immune intraepithelial lymphocytes (IELs) and may play a role in innate immunity
competence of CD4 T cells.
14–16
Some studies in mice provide experimental against microbial invasions, immune surveillance of malignancies, and
evidence supporting a role of CD8 T cells in protective immunity against even skin repair after damage.
25,26
Peripheral γδ T cells circulating in the
TB,
6,17,18
whereas others have reported the controversial data arguing against blood and lymphoid tissues appear to behave as both innate and
the role of CD8 T cells in immune protection against M. tuberculosis adaptive immune cells.
24-27
Circulating Vγ2Vδ2 (also called Vγ9Vδ2) T cells
infection.
7,19–23
It is also likely that CD8 T cells are important for controlling exist only in primates, and in humans constitute 60–95% of total blood
chronic TB rather than acute-phase M. tuberculosis infection. γδ T cells. Vγ2Vδ2 T cells in humans and non-human primates can
recognize phosphoantigen from some bacteria, such as M. tuberculosis,
and possess both innate and adaptive immune features.
24–27
The finding
Zheng W Chen, MD, PhD, is a Full Professor of Immunology and Microbiology and Director of the
Center for Primate Biomedical Research at the University of Illinois College of Medicine, Chicago.
that ‘unprimed’ Vγ2Vδ2 T cells can recognize and react to wide ranges of
He was previously an Associate Professor at Harvard. His primary research interests are focused on non-peptide ligands with the capability of ‘naïve’ production of cytokines
cellular and molecular aspects of T-cell immune responses to infections with AIDS viruses,
has been interpreted as a pattern-recognition-like feature of innate
Mycobacterium tuberculosis, and AIDS virus–mycobacterial co-infection using non-human primates
as model systems. Dr Chen has recently expanded his research program to T-cell-based
immune cells.
immunotherapeutics and vaccine modalities for AIDS, tuberculosis, and biodefense-related
endeavors. He has also developed an innovative nanotechnology-based research platform to study
On the other hand, the capacity of Vγ2Vδ2 T cells to undergo major clonal
nano-medicine and nano-immunology.
expansion in infections has been proposed as an adaptive (memory-type)
E:
zchen@uic.ed
immune response of these γδ T cells.
24
Vγ2Vδ2 T cells are unique in their
ability to massively expand during various bacterial and protozoal
20 © TOUCH BRIEFINGS 2008
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58 |
Page 59 |
Page 60 |
Page 61 |
Page 62 |
Page 63 |
Page 64 |
Page 65 |
Page 66 |
Page 67 |
Page 68 |
Page 69 |
Page 70 |
Page 71 |
Page 72 |
Page 73 |
Page 74 |
Page 75 |
Page 76