T cell independent antigens

SUMMARYIL-5 is a major factor inducing differentiation of B lymphocytes into immunoglobulin-producing cells as well as a main regulator of eosinophils. Recently, we have shown that peripheral blood mononuclear cells (PBMC) from patients with alveolar echinococcosis (AE) express IL-5 mRNA after stimulation with crude Echinococcus multilocularis (E.m.) antigen. To characterize the observed response in lymphocyte subpopulations, we cultured patients' PBMC in the presence of E.m. crude antigen for 18 h. PBMC were separated from seven patients by fluorescence-activated cell sorting (EPICSorter) into CD4 + and CD8 + subpopulations and from an additional seven patients by magnetic cell sorting (MACS) into CD4 + , CD8 + and the CD4 + /CD8 + depleted fractions. mRNA was detected by reverse transcriptasepolymerase chain reaction (RT-PCR) for the cytokines IFN-g, IL-2, IL-3, IL-4, IL-5, IL-6, IL-10, as well as for b-actin as control. IL-4 and IFN-g expression was positive in all of the patients in the stimulated CD4 + subgroup. IL-5 mRNA expression was detected in eight out of 14 CD4 + samples (58%) and not observed in the other subpopulations, or the unstimulated and healthy controls. Co-expression of other Th2 cytokines in the eight patients expressing IL-5 mRNA was found in five patients for IL-3 and in seven for IL-10. Expression of IL-5 and both Th2 cytokines (IL-3 and IL-10) was only observed in patients judged as critically ill. Out of the six patients who were regarded as cured after radical operation or as stabilized with or without chemotherapy, only two expressed IL-5. Out of those eight patients considered as critically ill, six expressed IL-5 mRNA and five of these co-expressed IL-3 and IL-10. Thus, we conclude that specific antigenic challenge of PBMC from patients with active or previous AE induces an IL-5 response of CD4 + lymphocytes. The expression of Th2-type interleukin mRNA is significantly more frequent in patients clinically judged as progressive. Furthermore, IgE was elevated only in patients regarded as critically ill (six out of eight). In none of the patients were eosinophils elevated. These data support a Th2-type immune response in patients with chronic E. multilocularis infection.

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“…Nonetheless, non-peptide antigens presented via CD1 might play an important role in the development of the Th2-type response [43,44].…”

Section: Discussionmentioning

confidence: 99%

IL-5 expressed by CD4+ lymphocytes from Echinococcus multilocularis-infected patients

Jenne

Kilwinski

Scheffold

et al. 1997

Clinical and Experimental Immunology

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“…Antigens can be classified as either T lymphocyte dependent (TD) or T lymphocyte independent (TI) with regard to their capacity for antibody induction (46). In the immune response to a TD antigen, a variety of cells are involved in the development of antibody responses.…”

Section: Discussionmentioning

confidence: 99%

Single Amino Acid Modification of Adeno-Associated Virus Capsid Changes Transduction and Humoral Immune Profiles

DiPrimio

Bowles

et al. 2012

J Virol

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Adeno-associated virus (AAV) vectors have the potential to promote long-term gene expression. Unfortunately, humoral immunity restricts patient treatment and in addition provides an obstacle to the potential option of vector readministration. In this study, we describe a comprehensive characterization of the neutralizing antibody (NAb) response to AAV type 1 (AAV1) through AAV5 both in vitro and in vivo. These results demonstrated that NAbs generated from one AAV type are unable to neutralize the transduction of other types. We extended this observation by demonstrating that a rationally engineered, muscle-tropic AAV2 mutant containing 5 amino acid substitutions from AAV1 displayed a NAb profile different from those of parental AAV2 and AAV1. Here we found that a single insertion of Thr from AAV1 into AAV2 capsid at residue 265 preserved high muscle transduction, while also changing the immune profile. To better understand the role of Thr insertion at position 265, we replaced all 20 amino acids and evaluated both muscle transduction and the NAb response. Of these variants, 8 mutants induced higher muscle transduction than AAV2. Additionally, three classes of capsid NAb immune profile were defined based on the ability to inhibit transduction from AAV2 or mutants. While no relationship was found between transduction, amino acid properties, and NAb titer or its cross-reactivity, these studies map a critical capsid motif involved in all steps of AAV infectivity. Our results suggest that AAV types can be utilized not only as templates to generate mutants with enhanced transduction efficiency but also as substrates for repeat administration.A deno-associated virus (AAV) vectors have been safely and successfully used in phase I clinical trials (39,40,54). In particular, therapeutic effects have been achieved in patients with Leber's congenital amaurosis and hemophilia B. Among 30 patients with Leber's congenital amaurosis, 28 demonstrated remarkably improved eyesight after AAV type 2 (AAV2) delivery of the rpe65 gene to the retina. Regarding the recent hemophilia B trial, all six patients had therapeutic factor IX (FIX) expression within a beneficial 1% to 8% of normal levels as long as 18 months after intravenous delivery of an AAV vector encoding an optimized FIX cassette (54).AAV is a nonenveloped, single-stranded DNA virus that requires a helper virus, such as adenovirus (Ad) or herpes simplex virus, for efficient replication. Despite the lack of inflammation or other AAV-associated complications following administration of AAV2 vectors in several organs, neutralizing antibody (NAb) titers against the AAV2 capsid were found to be significantly increased following vector administration, particularly in the lung, muscle, and liver (7, 8, 43-45, 49, 54, 63). NAbs in circulation are able to block AAV transduction after systemic administration. Recently, Manno et al. (44) performed a phase I study of AAV-mediated FIX transgene delivery in patients with hemophilia B, in which one patient with a higher preexisting NAb ti...

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“…1a,25(OH) 2 D 3 (suspended in arachid oil) or 50 ll arachid oil, until the end of the experiment. Our treatment was based on previous observations where long-term treatment with 1,25-dihydroxyvitamin D 3 or an analogue were necessary to observe major shifts in the immune system [41]. At the age of 8 weeks, the mice were immunized with Pneumovax J .…”

Section: Treatment Of Micementioning

confidence: 99%

“…Caps-PS are classified as thymus independent type 2 (TI-2) antigens, meaning that they are able to stimulate antibody production in the absence of MHC class IIrestricted T lymphocyte help [3,4]. However, T lymphocytes do modulate the anti-caps-PS antibody response: CD4 + T lymphocytes have a stimulatory effect, whereas CD8 + T lymphocytes have an inhibitory effect [5].…”

Section: Introductionmentioning

confidence: 99%

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1α,25-Dihydroxyvitamin D3 modulates the murine antibody response to pneumococcal capsular polysaccharide serotype 3 through IL-12

Jeurissen¹,

Etten²,

Overbergh³

et al. 2005

Eur. J. Immunol.

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1a, 25(OH) 2 D 3 ] is a steroid hormone that regulates calcium metabolism. Besides, 1a,25(OH) 2 D 3 also has pronounced immunomodulatory effects: it strongly inhibits dendritic cell (DC) maturation and impairs IL-12 production. We studied the effect of 1a,25(OH) 2 D 3 on the antibody response to pneumococcal capsular polysaccharide (caps-PS) serotype 3. 1a,25(OH) 2 D 3 inhibited the IgG2a antibody response to caps-PS serotype 3. Besides, 1a,25(OH) 2 D 3 also inhibited IL-12 production and maturation of DC. Anti-IL-12 and exogenous IL-12, respectively, inhibited and stimulated the IgG2a antibody response to caps-PS serotype 3. Exogenous IL-12 abrogated the effect of 1a,25(OH) 2 D 3 on the IgG2a antibody response to caps-PS serotype 3, indicating that the effect of 1a,25(OH) 2 D 3 on the IgG2a antibody response to caps-PS serotype 3 was mediated through IL-12.In conclusion, we demonstrate that 1a,25(OH) 2 D 3 has an inhibitory effect on the IgG2a antibody response to caps-PS serotype 3, and that this effect was mediated trough IL-12.

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T cell independent antigens

Cited by 240 publications

References 53 publications

IL-5 expressed by CD4+ lymphocytes from Echinococcus multilocularis-infected patients

IL-5 expressed by CD4+ lymphocytes from Echinococcus multilocularis-infected patients

Single Amino Acid Modification of Adeno-Associated Virus Capsid Changes Transduction and Humoral Immune Profiles

1α,25-Dihydroxyvitamin D3 modulates the murine antibody response to pneumococcal capsular polysaccharide serotype 3 through IL-12

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