Mycolic acid-specific T cells protect against Mycobacterium tuberculosis infection in a humanized transgenic mouse model
- Northwestern University, United States
Figures
Figure 1
Development of DN1 T cells is dependent on the presence of group 1 CD1 molecules.
(A) Schematic diagram of DN1 TCR construct used to generate DN1Tg mice. (B) The presence of DN1 TCR in the genomic DNA of transgenic mice was examined by PCR using primers specific for TRAV13-2 and T…
Figure 2 with 1 supplement
CD1b-expressing hematopoietic cells are the major cell type that medicates the positive selection of DN1 T cells.
Bone marrow from DN1Tg and DN1Tg/hCD1Tg mice (in the Rag-deficient background) were adoptively transferred into irradiated CD45.1 congenic WT and hCD1Tg recipients and the development of DN1 T cells …
Figure 2—figure supplement 1
CD1 expression does not significantly affect the development of DN1 T cells.
Lymphocytes from the thymus and spleen of DN1Tg/hCD1Tg, DN1Tg/hCD1Tg/CD1d-/-, DN1Tg and DN1Tg/CD1d-/- mice (all in the Rag-deficient background) were analyzed for the presence of DN1 T cells (TCRβ+hV…
Figure 3
DN1 T cells acquire effector functions in response to MA-pulsed DC and Mtb-infected DC.
(A) DN1 T cells isolated from lymph nodes of DN1Tg/hCD1Tg/Rag-/- mice were co-cultured with un-pulsed or MA-pulsed WT or hCD1Tg DC and IFN-γ producing cells were determined by ELISPOT assays. (B) …
Figure 4
DN1 T cell-mediated control of Mtb is dependent on the antigen presentation by group 1 CD1-expressing DCs and IFN-γ production.
(A) CD1b expression on BMDM and BMDC was detected using flow cytometry. (B) BMDMs were in vitro infected with Mtb (MOI=5) and DN1 T cells were added 1 day after infection. After 48 hr co-culture, …
Figure 5
Activation of DN1 T cells is initiated in mediastinal lymph nodes after aerosol Mtb infection.
(A) 3x106 naïve DN1 T cells were adoptively transferred into Mtb infected CD45.1 congenic hCD1Tg mice at day 7 post-infection. CD69 expression was detected on DN1 T cells (hVβ5+TCRβ+) from the MLN, …
Figure 6
DN1 T cells are activated earlier than Ag85 specific CD4+ T cells after Mtb infection.
(A, B) 3x106 CFSE-labeled DN1 T cells and 3x106 CellTrace Violet-labeled P25 T cells were co-transferred into Mtb infected CD45.1 congenic hCD1Tg mice. CD69 expression, CFSE and CellTrace Violet …
Figure 7 with 1 supplement
DN1 T cells contribute to protective immunity against Mtb infection.
Effector DN1 T cells (5-7x106 cells) were transferred into hCD1Tg/Rag-/- or Rag-/- mice 1 day before infection. Mice were euthanized at 4 week post-infection. (A) The number of bacteria in the lung, …
Figure 7—figure supplement 1
Adoptive transfer of listeria LemA-specific M3-restricted D7 T cells does not confer protection against Mtb infection.
Effector D7 T cells (5x106 cells) were transferred into hCD1Tg/Rag-/- mice 1 day before infection. Bacterial load in the lung was measured at 4 week post-infection. Each symbol represents the …
