An ongoing in vivo immune response affects the abundancy and differentiation of lymphokine-activated killer cell precursors, but does not influence their broad spectrum target reactivity.
Abstract: Using a model of local lymph node (LN) immunization, we investigated the effect of in vivo Ir on the generation of lymphokine-activated killer (LAK) cells or their precursors. Ag used for immunization were SRBC, horse RBC, OVA, keyhole limpet hemocyanin, or CFA. Ag-draining LN, in the acute phase of the Ir, did not contain detectable LAK effector activity, nor an enhanced NK activity. After culture for 3 to 5 days in the absence of exogenously added IL-2, immunized LN cells developed a spontaneous LAK-like cytotoxicity. This activity represented a substantial fraction of the IL-2-generated LAK cytolysis and was mediated by a Thy-1+ cell population phenotypically indistinct from IL-2-induced LAK. Inclusion (on day 0 of culture) of antibodies to IL-2, IL-2R, IL-4, IL-6, IFN-gamma, or TNF suggests a marginal involvement of IL-2 and IL-4 in the generation of this response. LAK, induced in vitro by exogenously added IL-2, developed earlier in LN cells immunized with particle Ag (SRBC, horse RBC, and CFA), but not with protein Ag (OVA and keyhole limpet hemocyanin). This effect was not mediated by endogenous IL-4. During further culture time in the presence of a saturating IL-2 concentration, similar levels of LAK activity were generated in naive and immunized LN cells. This agrees with the similar or slightly higher LAK precursor frequencies in immunized versus naive LN as assessed by limiting dilution experiments. Considering the 2.7-fold to 18-fold increase in cell content of the immunized LN, due to a recruitment and expansion of Ag-reactive B and T lymphocytes, a de novo generation of LAK precursors at the site of the Ir, and resulting from the Ir, must be assumed. In conclusion, our results suggest an interrelation between immune reactivity and LAK responses.
Publication Date: 1989-08-15 PubMed ID: 2787365
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This study probes into how ongoing immune responses in a living organism might affect the generation and activities of “lymphokine-activated killer” (LAK) cells. Findings reveal that while immune responses can increase the number and affect the differentiation of LAK cells, these responses do not change these cells’ broad spectrum target reactivity.
About the Research
The study used local lymph node (LN) immunization to discover the effect of immune responses on the initiation and formation of lymphokine-activated killer cells or their originators. Different Antigens (Ag), comprised of sheep red blood cells (SRBC), horse red blood cells (RBC), ovalbumin (OVA), keyhole limpet hemocyanin, or complete Freund’s adjuvant (CFA) were administered for immunization.
Findings and Outcomes
- The antigen-draining lymph nodes, during the acute phase of the immune response, were found to contain neither noticeable LAK effector activity nor heightened Natural Killer (NK) activity.
- On culture for 3-5 days devoid of exogenously added IL-2, the immunized lymph node cells developed a spontaneous LAK-like cytotoxicity.
- The cells responsible for the cytotoxicity were similar in phenotype to IL-2 induced LAK. They belong to the Thy-1+ cell population.
- During the initial part of the culture process, antibodies to IL-2, IL-2R, IL-4, IL-6, IFN-gamma, or TNF were included, suggesting the participation of IL-2 and IL-4 in the generation of this cytotoxic response is minimal.
Influence of Antigen Types and IL-2
- The research found that LAK cells, induced by adding exogenous IL-2, matured faster in lymph nodes (LN) immunized with particle antigens (like SRBC, horse RBC, and CFA), but not with protein antigens (like OVA & keyhole limpet hemocyanin).
- Over extended culture periods with high IL-2 concentrations, similar quantities of LAK activity were seen in both naive and immunized lymph nodes.
- Immunized lymph nodes depicted equal or slightly more LAK precursor frequencies as compared to naive ones, as evaluated by limiting dilution experiments.
Implications of the Findings
- Considering the 2.7 to 18 times increase in cell content of immunized lymph nodes, brought on by the recruitment and amplification of antigen-reactive B and T lymphocytes, it’s inferable that there’s a novel generation of LAK precursors at the site of immune response.
- In conclusion, the research implies a correlation between immune reactivity and LAK responses.
Cite This Article
APA
Vanhaesebroeck B, Grooten J, Fiers W.
(1989).
An ongoing in vivo immune response affects the abundancy and differentiation of lymphokine-activated killer cell precursors, but does not influence their broad spectrum target reactivity.
J Immunol, 143(4), 1396-1402.
Publication
Researcher Affiliations
- Laboratory of Molecular Biology, State University, Gent, Belgium.
MeSH Terms
- Animals
- Cell Differentiation
- Cell Line
- Cytotoxicity, Immunologic
- Erythrocyte Transfusion
- Female
- Freund's Adjuvant / immunology
- Hemocyanins / immunology
- Horses
- Interleukin-2
- Killer Cells, Natural / immunology
- Killer Cells, Natural / physiology
- Leukocyte Count
- Lymph Nodes / immunology
- Lymphocyte Activation
- Mice
- Mice, Inbred BALB C
- Ovalbumin / immunology
- Sheep
- Stem Cells / immunology
- Stem Cells / physiology
- Tumor Cells, Cultured
Citations
This article has been cited 2 times.- Matera L, Bellone G, Lebren JJ, Kelly PA, Hooghe Peters EL, Di Celle PF, Foa R, Contarini M, Avanzi G, Asnaghi V. Role of prolactin in the in vitro development of interleukin-2-driven anti-tumoural lymphokine-activated killer cells.. Immunology 1996 Dec;89(4):619-26.
- Laatikainen A, Schultz-Suhonen L, Mäntyjärvi R. Effect of interferon gamma on the sensitivity of bovine-papilloma-virus(BPV1)-transformed cell lines to cell-mediated cytotoxicity.. Cancer Immunol Immunother 1992;35(3):205-10.
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