Coadministration of interleukins 7 and 15 with bacille Calmette-Guérin mounts enduring T cell memory response against Mycobacterium tuberculosis.
BACKGROUND
The bacille Calmette-Guérin (BCG) vaccine renders protection against tuberculosis in childhood but not in adulthood. This may be due to its failure to induce long-lasting memory T cells. T cell memory is dependent on crucial cytokine signals during the priming phases. Therefore, coadministering the BCG vaccine with cytokines may improve its efficacy.


METHODS
A combination of the cytokines interleukin 7 (IL-7) and interleukin 15 (IL-15) or a combination of the cytokines interleukin 1 (IL-1), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-alpha), which are known to influence memory T cell generation, were administered along with BCG to mice. The animals were rested for a period of 240 d before they were challenged with Mycobacterium tuberculosis. Five weeks later, they were killed to study the T cell memory response.


RESULTS
Administration of IL-7 and IL-15, but not IL-1, IL-6, and TNF-alpha, with BCG resulted in an improved CD4 and CD8 T cell memory response. Mice injected with BCG supplemented with IL-7 and IL-15 showed enhanced T cell proliferation, T helper 1-type cytokine production, and an increased pool of multifunctional M. tuberculosis-specific memory T cells. Furthermore, there was a statistically significant reduction in the mycobacterial burden in the lungs.


CONCLUSIONS
Our results indicate that supplementation of the BCG vaccine with IL-7 and IL-15 would substantially improve its efficacy by enhancing the T cell memory response.
Singh
Vijender
V
Institute of Microbial Technology, Chandigarh, India.
Gowthaman
Uthaman
U
Jain
Shweta
S
Parihar
Pankaj
P
Banskar
Sunil
S
Gupta
Pushpa
P
Gupta
Umesh D
UD
Agrewala
Javed N
JN
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D015169:Colony Count, Microbial; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D007375:Interleukin-1 / Q000008:administration & dosage; D019409:Interleukin-15 / Q000008:administration & dosage*; D015850:Interleukin-6 / Q000008:administration & dosage; D015851:Interleukin-7 / Q000008:administration & dosage*; D008168:Lung / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009163:Mycobacterium bovis / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D000276:Adjuvants, Immunologic; D007375:Interleukin-1; D019409:Interleukin-15; D015850:Interleukin-6; D015851:Interleukin-7; D014409:Tumor Necrosis Factor-alpha