Differential CD28 and Inducible Costimulatory Molecule Signaling Requirements for Protective CD4<sup>+</sup>T-Cell-Mediated Immunity against Genital Tract<i>Chlamydia trachomatis</i>Infection

Marks, Ellen; Verolin, Martina; Stensson, Anneli; Lycke, Nils

doi:10.1128/iai.00465-07

Cited by 41 publications

(39 citation statements)

References 59 publications

(53 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The expression of Foxp3 also corresponded to the number of Th1 cells in that site. These authors further noted that depleting TRCs increased immunopathology in the upper genital tract [Marks et al, 2007]. Similar to the trachoma study above, only transcripts of FOXP3 were followed in tissue as evidence of the presence of TRCs.…”

Section: Characterization Of T Regulatory Cells In Mice and Humanssupporting

confidence: 64%

The Role of T Regulatory Cells in Chlamydia trachomatis Genital Infection

Kelly¹,

Champion²,

Jiang³

2012

Chlamydia

View full text Add to dashboard Cite

Section: Characterization Of T Regulatory Cells In Mice and Humanssupporting

confidence: 64%

The Role of T Regulatory Cells in Chlamydia trachomatis Genital Infection

Kelly¹,

Champion²,

Jiang³

2012

Chlamydia

View full text Add to dashboard Cite

“…Determinations of antibody levels in mouse serum, BAL and vaginal secretions were done by ELISA as described previously (Eliasson et al, 2008;Forsell et al, 2007;Marks et al, 2007). Briefly, ELISA plates (Nunc) were coated with 1 mg insect cell (S2)-produced YU2gp120 ml 21 in 100 ml PBS at 4 uC overnight.…”

Section: Methodsmentioning

confidence: 99%

CTA1-DD adjuvant promotes strong immunity against human immunodeficiency virus type 1 envelope glycoproteins following mucosal immunization

Sundling

Schön

Mörner

et al. 2008

Journal of General Virology

View full text Add to dashboard Cite

Strategies to induce potent and broad antibody responses against the human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins (Env) at both systemic and mucosal sites represent a central goal for HIV-1 vaccine development. Here, we show that the non-toxic CTA1-DD adjuvant promoted mucosal and systemic humoral and cell-mediated immune responses following intranasal (i.n.) immunizations with trimeric or monomeric forms of HIV-1 Env in mice and in nonhuman primates. Env-specific IgG subclasses in the serum of immunized mice reflected a balanced Th1/Th2 type of response. Strikingly, i.n. immunizations with Env and the CTA1-DD adjuvant induced substantial levels of mucosal anti-Env IgA in bronchial alveolar lavage and also detectable levels in vaginal secretions. By contrast, parenteral immunizations of Env formulated in Ribi did not stimulate mucosal IgA responses, while the two adjuvants induced a similar distribution of Env-specific IgG-subclasses in serum. A single parenteral boost with Env in Ribi adjuvant into mice previously primed i.n. with Env and CTA1-DD, augmented the serum anti-Env IgG levels to similar magnitudes as those observed after three intraperitoneal immunizations with Env in Ribi. The augmenting potency of CTA1-DD was similar to that of LTK63 or CpG oligodeoxynucleotides (ODN). However, in contrast to CpG ODN, the effect of CTA1-DD and LTK63 appeared to be independent of MyD88 and toll-like receptor signalling. This is the first demonstration that CTA1-DD augments specific immune responses also in non-human primates, suggesting that this adjuvant could be explored further as a clinically safe mucosal vaccine adjuvant for humoral and cell-mediated immunity against HIV-1 Env. INTRODUCTIONBecause the majority of natural human immunodeficiency virus type 1 (HIV-1) transmissions occur via mucosal membranes an effective prophylactic vaccine should stimulate immune responses that are active at the portal site for viral entry (Gupta & Klasse, 2006;Mestecky et al., 2005). Vaccine-induced neutralizing antibodies (NAbs) that interfere with viral entry have been found to be the protective correlates of many other prophylactic antiviral vaccines (Parren et al., 2001;Wicker et al., 2007;Zignol et al., 2004). An HIV-1 vaccine that prevents or limits virus replication in the mucosa should reduce the risk of systemic viral dissemination (Haase, 2005;Maher et al., 2005;Mazanec et al., 1992) and may reduce the risk of human-to-human transmission (Kozlowski & Neutra, 2003;Mascola, 2003;Neutra & Kozlowski, 2006). However, the development of mucosal vaccines has been slow, owing mainly to the lack of safe and effective mucosal adjuvants. Furthermore, there is insufficient knowledge as to the best route for immunization of the genital tract: i.n., local vaginal, rectal or parenteral. Also, combinations of regimens, such as mucosal priming followed by systemic boost, or, systemic priming followed by mucosal boost, have not been exhaustively investigated (Vajdy et al., 2004). Finally, an overriding problem to ...

show abstract

“…More recently, Tregs were demonstrated to enhance host resistance to mucosal fungal infection via the promotion of Th17 responses (27). Although several murine and human studies report that Chlamydia infection induces expansion of Foxp3 + Tregs (28)(29)(30), our understanding about the role of Tregs during Chlamydia infection remains rudimentary.…”

mentioning

confidence: 99%

CD4+CD25+Foxp3+ Regulatory T Cells Promote Th17 Responses and Genital Tract Inflammation upon Intracellular Chlamydia muridarum Infection

Moore-Connors

Fraser

Halperin

et al. 2013

The Journal of Immunology

View full text Add to dashboard Cite

The functional role of CD4+CD25+Foxp3+ regulatory T cells (Tregs) in host responses to intracellular bacterial infection was investigated in an in vitro coculturing system and a murine model of Chlamydia muridarum genital tract infection. Remarkably, C. muridarum infection subverted the immune suppressive role of CD4+CD25+Foxp3+ Tregs; instead of hampering immune responses, Tregs not only promoted Th17 differentiation from conventional CD4+ T cells but also themselves converted into proinflammatory Th17 cells in both in vitro and in vivo settings. Anti-CD25 mAb PC61 treatment to deplete ∼50% of pre-existing Tregs prior to C. muridarum genital tract infection markedly reduced the frequency and the total number of Th17 but not Th1 CD4+ cells at both immune induction and memory phases. Most importantly, Treg-depleted mice displayed significantly attenuated inflammation, neutrophil infiltration, and reduced severity of oviduct pathology upon C. muridarum genital infection. To our knowledge, this is the first report demonstrating that the level of pre-existing CD4+CD25+Foxp3+ Tregs in Chlamydia-infected hosts has a major impact on the development Chlamydia-associated diseases.

show abstract

Differential CD28 and Inducible Costimulatory Molecule Signaling Requirements for Protective CD4⁺T-Cell-Mediated Immunity against Genital TractChlamydia trachomatisInfection

Abstract: Th1 cells and gamma interferon (IFN-␥

Cited by 41 publications

References 59 publications

The Role of T Regulatory Cells in Chlamydia trachomatis Genital Infection

The Role of T Regulatory Cells in Chlamydia trachomatis Genital Infection

CTA1-DD adjuvant promotes strong immunity against human immunodeficiency virus type 1 envelope glycoproteins following mucosal immunization

CD4+CD25+Foxp3+ Regulatory T Cells Promote Th17 Responses and Genital Tract Inflammation upon Intracellular Chlamydia muridarum Infection

Contact Info

Product

Resources

About

Differential CD28 and Inducible Costimulatory Molecule Signaling Requirements for Protective CD4+T-Cell-Mediated Immunity against Genital TractChlamydia trachomatisInfection

Abstract: Th1 cells and gamma interferon (IFN-␥

Cited by 41 publications

References 59 publications

The Role of T Regulatory Cells in Chlamydia trachomatis Genital Infection

The Role of T Regulatory Cells in Chlamydia trachomatis Genital Infection

CTA1-DD adjuvant promotes strong immunity against human immunodeficiency virus type 1 envelope glycoproteins following mucosal immunization

CD4+CD25+Foxp3+ Regulatory T Cells Promote Th17 Responses and Genital Tract Inflammation upon Intracellular Chlamydia muridarum Infection

Contact Info

Product

Resources

About

Differential CD28 and Inducible Costimulatory Molecule Signaling Requirements for Protective CD4⁺T-Cell-Mediated Immunity against Genital TractChlamydia trachomatisInfection