Functional capacity of Mycobacterium tuberculosis-specific T cell responses in humans is associated with mycobacterial load1
High antigen load in chronic viral infections has been associated with impairment of antigen-specific T cell responses; however, the relationship between antigen load in chronic Mycobacterium tuberculosis ( Mtb ) infection and functional capacity of Mtb -specific T cells in humans is not clear. We c...
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Published in | The Journal of immunology (1950) Vol. 187; no. 5; pp. 2222 - 2232 |
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Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
20.07.2011
|
Online Access | Get full text |
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Summary: | High antigen load in chronic viral infections has been associated with impairment of antigen-specific T cell responses; however, the relationship between antigen load in chronic
Mycobacterium tuberculosis
(
Mtb
) infection and functional capacity of
Mtb
-specific T cells in humans is not clear. We compared
Mtb
-specific T cell-associated cytokine production and proliferative capacity in peripheral blood from adults with progressively higher mycobacterial loads, i.e., persons with latent
Mtb
infection (LTBI), with smear − pulmonary tuberculosis (TB), and with smear+ TB. Patients with smear+ TB had decreased polyfunctional IFN-γ
+
IL-2
+
TNF-α
+
and IL-2-producing specific CD4 T cells and increased TNF-α-single positive cells, when compared with smear − TB and LTBI. TB patients also had increased frequencies of
Mtb
-specific CD8 T cells, compared with LTBI.
Mtb
-specific CD4 and CD8 T cell proliferative capacity was profoundly impaired in individuals with smear+ TB, and correlated positively with
ex vivo
IFN-γ
+
IL-2
+
TNF-α
+
CD4 T cells, and inversely with TNF-α single-positive CD4 T cells. During 6 months of anti-TB treatment, specific IFN-γ
+
IL-2
+
TNF-α
+
CD4 and CD8 T cells increased, whereas TNF-α- and IFN-γ-single positive T cells decreased. These results suggest progressive impairment of
Mtb
-specific T cell responses with increasing mycobacterial load, and recovery of responses during therapy. Furthermore, these data provide a link between specific cytokine-producing subsets and functional capacity of
Mtb
-specific T cells, and between the presence of specific CD8 T cells
ex vivo
and active TB disease. Taken together, these data have potentially significant applications for diagnosis of TB and for identification of T cell correlates of TB disease progression. |
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ISSN: | 0022-1767 1550-6606 |
DOI: | 10.4049/jimmunol.1101122 |