CD40 Ligand Trimer Enhances the Response of CD8+ T Cells to <i>Mycobacterium tuberculosis</i>

Samten, Buka; Wizel, Benjamin; Shams, Homayoun; Weis, Stephen E.; Klucar, Peter; Wu, Shijie; Vankayalapati, Ramakrishna; Thomas, Elaine K.; Okada, Satoshi; Krensky, Alan M.; Barnes, Peter F.

doi:10.4049/jimmunol.170.6.3180

Cited by 26 publications

(26 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Phagocytes, not lymphocytes, have generally been implicated as the important lines of defense against bacteria (21). The roles of CTL and NK cells have been more narrowly confined to tumor and antiviral immunity and certain specific bacterial and parasitic infections (46,63). GNLY has broad-based clinical relevance as a diagnostic (biomarker) and potential therapeutic in entities as diverse as transplant rejection, cancer, and infectious diseases (6, 17-25, 30 -32).…”

Section: Discussionmentioning

confidence: 99%

Granulysin-Mediated Tumor Rejection in Transgenic Mice

Huang

Lyu

Clayberger

et al. 2007

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

Granulysin (GNLY) is a cytolytic molecule expressed by human CTL and NK cells with activity against a variety of tumors and microbes, including Mycobacterium tuberculosis. Although the molecular mechanism of GNLY-induced apoptosis of Jurkat T cells is well defined in vitro, no direct evidence for its in vivo effects has been demonstrated. Because there is no murine homologue of GNLY, we generated mice expressing GNLY using a bacterial artificial chromosome containing the human GNLY gene and its 5′ and 3′ flanking regions. GNLY is expressed in leukocytes from transgenic mice with similar kinetics as in PBMC from humans: GNLY is constitutively expressed in NK cells and, following stimulation through the TCR, appears in T lymphocytes 8–10 days after activation. Both forms of GNLY (9 and 15 kDa) are produced by activated T cells, whereas the 15-kDa form predominates in freshly isolated NK cells from transgenic animals. GNLY mRNA is highest in spleen, with detectable expression in thymus and lungs, and minimal expression in heart, kidney, liver, muscle, intestine, and brain. Allospecific cell lines generated from GNLY transgenic animals showed enhanced killing of target cells. In vivo effects of GNLY were evaluated using the syngeneic T lymphoma tumor C6VL. GNLY transgenic mice survived significantly longer than nontransgenic littermates in response to a lethal tumor challenge. These findings demonstrate for the first time an in vivo effect of GNLY and suggest that GNLY may prove a useful therapeutic modality for the treatment of cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

Granulysin-Mediated Tumor Rejection in Transgenic Mice

Huang

Lyu

Clayberger

et al. 2007

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

show abstract

“…PGE2 production and expansion of Tregs may be also mediated in part through cell-to-cell contact between activated T-cells and M. tuberculosisinfected monocytes. Ligation of CD40 induces PGE2 production and favors development of Tregs [47,48], and CD40:CD40L interactions are observed in the human immune response to M. tuberculosis [49]. ICOS:ICOS ligand interactions also induce expansion of Tregs [50].…”

Section: Increased Percentages Of Tregs In Tuberculosis Patientsmentioning

confidence: 99%

Mannose‐capped lipoarabinomannan‐ and prostaglandin E2‐dependent expansion of regulatory T cells in human Mycobacterium tuberculosis infection

et al. 2008

Self Cite

View full text Add to dashboard Cite

We evaluated the role of regulatory T cells (CD4 + CD25 + Foxp3 + cells, Tregs) in human Mycobacterium tuberculosis infection. Tregs were expanded in response to M. tuberculosis in healthy tuberculin reactors, but not in tuberculin-negative individuals. The M. tuberculosis mannose-capped lipoarabinomannan (ManLAM) resulted in regulatory T cell expansion, whereas the M. tuberculosis 19-kDa protein and heat shock protein 65 had no effect. Anti-IL-10 and anti-TGF-b alone or in combination, did not reduce expansion of Tregs. In contrast, the cyclooxygenase enzyme-2 inhibitor NS398 significantly inhibited expansion of Tregs, indicating that prostaglandin E2 (PGE2) contributes to Treg expansion. Monocytes produced PGE2 upon culturing with heat-killed M. tuberculosis or ManLAM, and T cells from healthy tuberculin reactors enhanced PGE2 production by monocytes. Expanded Tregs produced significant amounts of TGF-b and IL-10 and depletion of Tregs from PBMC of these individuals increased the frequency of M. tuberculosis-responsive CD4 + IFN-c cells. Culturing M. tuberculosis-expanded Tregs with autologous CD8 + cells decreased the frequency of IFN-c + cells. Freshly isolated PBMC from tuberculosis patients had increased percentages of Tregs, compared to healthy tuberculin reactors. These findings demonstrate that Tregs expand in response to M. tuberculosis through mechanisms that depend on ManLAM and PGE2.

show abstract

“…In vitro ligation of CD40 on the surface of DCs by soluble CD40L or CD40L-transfected L cells (CD40L ϩ -L cells) stimulates DCs to increase expression of costimulatory and MHC molecules, produce IL-12 and -15, and prevent apoptosis (18 -20). Because of these properties, CD40L has been used to generate mature DCs as APCs to expand CD8 ϩ CTL specific for viral and bacterial Ags (18,(21)(22)(23).…”

Section: Engue Viruses (Dv)mentioning

confidence: 99%

CD40 Ligand Enhances Dengue Viral Infection of Dendritic Cells: A Possible Mechanism for T Cell-Mediated Immunopathology

Sun

Celluzzi

Marovich

et al. 2006

The Journal of Immunology

View full text Add to dashboard Cite

We have previously shown that dengue virus (DV) productively infects immature human dendritic cells (DCs) through binding to cell surface DC-specific ICAM-3-grabbing nonintegrin molecules. Infected DCs are apoptotic, refractory to TNF-␣ stimulation, inhibited from undergoing maturation, and unable to stimulate T cells. In this study, we show that maturation of infected DCs could be restored by a strong stimulus, CD40L. Addition of CD40L significantly reduced apoptosis of DCs, promoted IL-12 production, and greatly elevated the IFN-␥ response of T cells, but yet did not restore T cell proliferation in MLR. Increased viral infection of DCs was also observed; however, increased infection did not appear to be mediated by DC-specific ICAM-3-grabbing nonintegrin, but rather was regulated by decreased production of IFN-␣ and decreased apoptotic death of infected DCs. Because CD40L is highly expressed on activated memory (but not naive) T cells, the observation that CD40L signaling results in enhanced DV infection of DC suggests a possible T cell-dependent mechanism for the immune-mediated enhancement of disease severity associated with some secondary dengue infections.

show abstract

CD40 Ligand Trimer Enhances the Response of CD8+ T Cells to Mycobacterium tuberculosis

Cited by 26 publications

References 62 publications

Granulysin-Mediated Tumor Rejection in Transgenic Mice

Granulysin-Mediated Tumor Rejection in Transgenic Mice

Mannose‐capped lipoarabinomannan‐ and prostaglandin E2‐dependent expansion of regulatory T cells in human Mycobacterium tuberculosis infection

CD40 Ligand Enhances Dengue Viral Infection of Dendritic Cells: A Possible Mechanism for T Cell-Mediated Immunopathology

Contact Info

Product

Resources

About