Method for inducing formation and proliferation of mucosal tissue resident memory T cells

A memory and cell technology, applied in the field of inducing the formation and proliferation of mucosal resident memory T cells, can solve the problem of inability to induce the formation and proliferation of mucosal TRM

Pending Publication Date: 2020-04-17
SHANGHAI PUBLIC HEALTH CLINICAL CENT
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Classical vaccination methods (such as intramuscular injection, intradermal injection, subcutaneous injection, etc.) can effectively expand effector memory T cells and central memory T cells in vivo, but systemic immunity and mucosal immunity are relatively independent. Classical vaccination methods Cannot effectively induce the formation and proliferation of mucosal TRMs in animal models
Due to the division of mucosal parts throughout the body into different immune compartments, vaccination at one mucosal site alone cannot effectively induce T cell expansion in other mucosal sites, for example, it is difficult to induce effective T cell proliferation in intestinal sites through nasal mucosal vaccination
However, vaccination through the intestine alone faces the challenges of digestive tract tolerance and digestion of immunogens by digestive enzymes

Method used

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  • Method for inducing formation and proliferation of mucosal tissue resident memory T cells
  • Method for inducing formation and proliferation of mucosal tissue resident memory T cells
  • Method for inducing formation and proliferation of mucosal tissue resident memory T cells

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Example 1: Evaluation of the effect of different vaccination procedures on inducing mucosal rectal memory T cells

[0034] C57 / BL6 mice were immunized with different immunization procedures, the immunogen was the model antigen ovalbumin (OVA), and the adjuvant was cholera toxin (Cholera Toxin, CT). Four weeks after the completion of the immunization (immune memory period) , to evaluate the induction of OVA by different inoculation procedures 257-264 Effects of specific rectal memory T cells. Chicken ovalbumin and cholera toxin used in this experiment were purchased from Sigma Company. The experimental steps are as follows:

[0035] (1) C57BL / 6 mice at the age of 6-8 weeks were randomly divided into 5 groups, which were named rectal + rectal group, nasal drip + nasal drip group, nasal drip + reproductive tract group, drip nasal + reproductive tract group, and Nasal + rectal group, nasal drop + rectal + rectal group.

[0036] (2) 24 hours before immunization, adopt OT...

Embodiment 2

[0043] Example 2: Effect evaluation of gp120-specific rectal TRM induced by "nasal drip priming and rectal boost"

[0044] Mice were immunized with the gp120 protein of the extramembrane region of the membrane protein of HIV-1 (AE2F strain) and CT, the first injection was inoculated through the nose, and the second injection was inoculated through the rectum. Four weeks after completion of the immunization (immune memory period), the induction effect of gp120-specific rectal resident memory T cells in the rectal site was evaluated. The experimental steps are as follows:

[0045] (1) C57BL / 6 mice aged 6-8 weeks were randomly divided into two groups, named control group and gp120 group, respectively.

[0046] (2) The mice were immunized with the immunogen gp120 and the adjuvant CT, and the specific immunization procedures are shown in Table 2. Each mouse was anesthetized by intraperitoneal injection of 100 microliters of 1% pentobarbital before intranasal instillation of immun...

Embodiment 3

[0052] Example 3: Evaluation of the effect of circulating activated T cells infiltrating into rectal tissue under the action of rectal immunization

[0053] The spleen and peripheral blood antigen-specific T cells activated by intranasal immunization were sorted out, adopted to recipient mice, and the infiltration effect of antigen-specific T cells into the rectal tissue was evaluated. The experimental steps are as follows:

[0054] (1) As described in Example 1, adopt OT-I cells to C57BL / 6 mice.

[0055] (2) The immunogen OVA and the adjuvant CT were instilled into the immunized mice through the nasal cavity, and the immunization dose was the same as that in Example 1.

[0056] (3) On the 7th day after immunization, the spleen and peripheral blood of the mice were collected, and OVA was sorted by magnetic bead sorting (brand: Miltenyi, item number: 130-048-801) 257-264 Specific (ie, CD45.1+ cells) T cells. The cells obtained by sorting were used as donor cells for subseque...

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Abstract

The invention relates to the field of mucosal immune cells, in particular to a method for inducing formation and proliferation of mucosal tissue resident memory T cells (TRM). The method at least comprises primary immunization of parts except intestinal tracts and enhanced immunization of the intestinal tracts, so that a large number of mucosal TRM are obtained and are used for preventing and treating mucosal invasion of pathogens. The primary immunization modes of the parts except the intestinal tracts at least comprise but are not limited to muscle inoculation, intracutaneous inoculation, subcutaneous inoculation, nasal drop inoculation, aerosol inhalation inoculation and sublingual inoculation. The immunity enhancing mode of the intestinal tract part comprises but is not limited to rectal intracavitary inoculation, and intestinal intracavitary inoculation is conducted through oral administration of enteric-coated vaccines.

Description

technical field [0001] The invention relates to the field of mucosal immune cells, in particular to a method for inducing the formation and proliferation of mucosal resident memory T cells. Background technique [0002] Human immunodeficiency virus (HIV) is a class of virus that seriously threatens public health. According to the HIV-1 prevalence data released by the United Nations Program on AIDS (UNAIDS), about 36.9 million people were infected with HIV-1 worldwide in 2017, of which 1.8 million were new cases, mainly through sexual contact including the genital tract and rectum Infection and transmission through mucosal routes, especially the rapid increase in the proportion of MSM (Man who have sex with man, MSM) infection. Epidemiological surveys show that the risk of male to male transmission of HIV is 1 / 10-1 / 600, which is much higher than the risk of heterosexual transmission of 1 / 200-1 / 1000. Therefore, blocking sexual transmission including rectal mucosa is the most ...

Claims

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Application Information

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IPC IPC(8): A61K39/00A61P31/00
CPCA61K39/00A61P31/00A61K2039/54A61K2039/542A61K2039/543Y02A50/30
Inventor 徐建青张晓燕贺倩
Owner SHANGHAI PUBLIC HEALTH CLINICAL CENT
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