Home Immunology Application of Long-term cultured Interferon-γ Enzyme-linked Immunospot Assay for Assessing Effector and Memory T Cell Responses in Cattle
Immunology JoVE (Open Access) Citable · DOI

Application of Long-term cultured Interferon-γ Enzyme-linked Immunospot Assay for Assessing Effector and Memory T Cell Responses in Cattle

DOI: 10.3791/52833-v
What you'll learn
  • Perform long-term culture of bovine PBMCs with mycobacterial antigens and IL-2
  • Execute IFN-γ ELISPOT assay protocol across three-day timeline
  • Differentiate central memory T cell responses via flow cytometry analysis
  • Measure anti-mycobacterial vaccine protective immunity in cattle
Protocol

Biopharma Insights Long-term cultured interferon-γ enzyme-linked immunospot assay is used as a measure of central memory responses and correlates with protective anti-mycobacterial vaccine responses. With this assay, peripheral blood mononuclear cells are stimulated with mycobacterial antigens and interleukin-2 for 14 days, enabling differentiation and expansion of central memory T cells.

Difficulty
advanced
Total time
~16 days (14-day culture + 3-day ELISPOT assay + analysis)
Model organism
Cattle (bovine peripheral blood mononuclear cells)
Biosafety
BSL-2

Steps

1
Establish long-term PBMC culture with antigens

Stimulate peripheral blood mononuclear cells with mycobacterial antigens and interleukin-2 for 14 days to enable central memory T cell expansion and differentiation.

▶ 01:40
2
Prepare ELISPOT plate coating and blocking

Coat ELISPOT plates with capture antibodies and apply blocking solution on day 1 of the assay protocol.

▶ 03:38
3
Add cultured cells to ELISPOT plates

Transfer stimulated PBMCs to prepared ELISPOT plates and incubate overnight to allow IFN-γ secretion and capture.

▶ 04:30
4
Isolate adherent cells from culture

Harvest and separate adherent cell populations from long-term cultured cells for downstream analysis.

▶ 05:15
5
Prepare samples for flow cytometry analysis

Aliquot cultured cells and stain with fluorescent antibodies for phenotypic characterization of T cell subsets.

▶ 05:37
6
Harvest cultured cells on day thirteen

Collect and prepare long-term cultured PBMC populations prior to final ELISPOT assay processing.

▶ 06:15
7
Add detection antibodies and enzyme substrate

Apply alkaline phosphatase-conjugated secondary antibodies and substrate solution to ELISPOT plates on day 3.

▶ 09:05
8
Prepare alkaline phosphatase enzyme solution

Dilute and prepare alkaline phosphatase-conjugated detection reagent for ELISPOT plate development.

▶ 10:05
9
Prepare and apply substrate solution

Mix substrate components and apply to ELISPOT plates to develop colorimetric signal at IFN-γ-secreting cell sites.

▶ 11:08
10
Scan and quantify ELISPOT plate spots

Use automated ELISPOT reader to image plates and count IFN-γ-secreting spot-forming cells.

▶ 11:55
11
Perform flow cytometry characterization

Analyze phenotypic markers on cultured T cells using multiparameter flow cytometry to identify memory subsets.

▶ 12:12
12
Interpret results and assess vaccine response

Correlate IFN-γ ELISPOT data with flow cytometry findings to measure central memory responses and predict anti-mycobacterial protective immunity.

▶ 12:25

🚨 Failure Case Library (1) + Submit your own case

critical
No Spots or Very Weak Signal
Few or no spots are visible after development, or spots are extremely faint and difficult to detect even though cytokine-secreting cells should be present.
💡 5 · ✓ 5
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