The Memory Immune Response to Tuberculosis

Paraquat (PQ) is a toxic non-selective herbicide. To date, the effect of PQ on memory immune response is still unknown. We investigated the impact of PQ on memory immune response. Adult C57BL/6 mice were subcutaneously injected with 2 mg/kg PQ, 20 mg/kg PQ or vehicle control every three days for two weeks. A single injection of keyhole limpet hemocyanin (KLH) at day four after the initial PQ treatment was used to induce a primary immune response; a second KLH challenge was performed at three months post the first KLH immunization to induce a secondary immune response. In steady state, treatment with 20 mg/kg PQ reduced the level of serum total IgG, but not that of IgM; treatment with 20 mg/kg PQ decreased the number of effector and memory lymphocytes, but not naïve or inactivated lymphocytes. During the primary immune response to KLH, treatment with 20 mg/kg PQ did not influence the proliferation of lymphocytes or expression of co-stimulatory molecules. Instead, treatment with 20 mg/kg PQ increased the apoptosis of lymphocytes at late stage, but not early stage of the primary immune response. During the secondary immune response to KLH, treatment with 20 mg/kg PQ reduced the serum anti-KLH IgG and KLH-responsive CD4 T cells and B cells. Moreover, effector or activated lymphocytes were more sensitive to PQ-induced apoptosis in vitro. Treatment with 2 mg/kg PQ did not impact memory immune response to KLH. Thus, treatment with 20 mg/kg PQ increased apoptosis of late stage effector cells to yield less memory cells and thereafter impair memory immune response, providing a novel understanding of the immunotoxicity of PQ.

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Shaping the CD4+ memory immune response against tuberculosis: the role of antigen persistence, location and multi-functionality

BioMolecular Concepts ◽

10.1515/bmc.2011.051 ◽

2012 ◽

Vol 3 (1) ◽

pp. 13-20 ◽

Cited By ~ 1

Author(s):

Lindsay Ancelet ◽

Joanna Kirman

Keyword(s):

Immune Response ◽

T Cells ◽

Rational Design ◽

Memory T Cells ◽

T Cell Response ◽

Intracellular Pathogens ◽

Memory T Cell ◽

Antigen Persistence ◽

Memory Immune Response

AbstractEffective vaccination against intracellular pathogens, such as tuberculosis (TB), relies on the generation and maintenance of CD4 memory T cells. An incomplete understanding of the memory immune response has hindered the rational design of a new, more effective TB vaccine. This review discusses how the persistence of antigen, the location of memory cells, and their multifunctional ability shape the CD4 memory T cell response against TB.

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CD8+ T Cells Participate in the Memory Immune Response to Mycobacterium tuberculosis

Infection and Immunity ◽

10.1128/iai.69.7.4320-4328.2001 ◽

2001 ◽

Vol 69 (7) ◽

pp. 4320-4328 ◽

Cited By ~ 89

Author(s):

Natalya V. Serbina ◽

JoAnne L. Flynn

Keyword(s):

Immune Response ◽

T Cells ◽

Mycobacterium Tuberculosis ◽

T Cell ◽

Acute Infection ◽

Cell Subset ◽

Ifn Γ ◽

Memory And Recall ◽

Memory Immune Response ◽

Activation Marker Cd69

ABSTRACT The contribution of CD8+ T cells to the control of tuberculosis has been studied primarily during acute infection in mouse models. Memory or recall responses in tuberculosis are less well characterized, particularly with respect to the CD8 T-cell subset. In fact, there are published reports that CD8+ T cells do not participate in the memory immune response to Mycobacterium tuberculosis. We examined the CD8+ T-cell memory and local recall response to M. tuberculosis. To establish a memory immunity model, C57BL/6 mice were infected with M. tuberculosis, followed by treatment with anti-mycobacterial drugs and prolonged rest. The lungs of memory immune mice contained CD4+ and CD8+ T cells with the cell surface phenotype characteristic of memory cells (CD69lowCD25low CD44high). At 1 week postchallenge withM. tuberculosis via aerosol, ≥30% of both CD4+ and CD8+ T cells in the lungs of immune mice expressed the activation marker CD69 and could be restimulated to produce gamma interferon (IFN-γ). In contrast, <6% of T cells in the lungs of naive challenged mice were CD69+ at 1 week postchallenge, and IFN-γ production was not observed at this time point. CD8+ T cells from the lungs of both naive and memory mice after challenge were cytotoxic toward M. tuberculosis-infected macrophages. Our data indicate that memory and recall immunity to M. tuberculosis is comprised of both CD4+ and CD8+ T lymphocytes and that there is a rapid response of both subsets in the lungs following challenge.

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Development of a Secondary Immune Response toMycobacterium tuberculosisIs Independent of Toll-Like Receptor 2

Infection and Immunity ◽

10.1128/iai.01076-10 ◽

2010 ◽

Vol 79 (3) ◽

pp. 1118-1123 ◽

Cited By ~ 11

Author(s):

Amanda McBride ◽

Kamlesh Bhatt ◽

Padmini Salgame

Keyword(s):

Immune Response ◽

T Cells ◽

Host Resistance ◽

Toll Like Receptor ◽

Response Phenotype ◽

Toll Like Receptor 2 ◽

Antigen Presenting ◽

Memory Immune Response

ABSTRACTPublished work indicates that the contribution of Toll-like receptor 2 (TLR2) to host resistance during acuteMycobacterium tuberculosisinfection is marginal. However, in these studies, TLR2 participation in the memory immune response toM. tuberculosiswas not determined. The substantialin vitroevidence thatM. tuberculosisstrongly triggers TLR2 on dendritic cells and macrophages to bring about either activation or inhibition of antigen-presenting cell (APC) functions, along with accumulating evidence that memory T cell development can be calibrated by TLR signals, led us to question the role of TLR2 in host resistance to secondary challenge withM. tuberculosis. To address this question, a memory immunity model was employed, and the response of TLR2-deficient (TLR2 knockout [TLR2KO]) mice following a secondary exposure toM. tuberculosiswas compared to that of wild-type (WT) mice based on assessment of the bacterial burden, recall response, phenotype of recruited T cells, and granulomatous response. We found that upon rechallenge withM. tuberculosis, both WT and TLR2KO immune mice displayed similarly enhanced resistance to infection in comparison to their naïve counterparts. The frequencies ofM. tuberculosis-specific gamma interferon (IFN-γ)-producing T cells, the phenotypes of recruited T cells, and the granulomatous responses were also similar between WT and TLR2KO immune mice. Together, the findings from this study indicate that TLR2 signaling does not influence memory immunity toM. tuberculosis.

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