Continuous cultivation of equine lymphocytes: evidence for occasional T cell-like maturation events in horses with hereditary severe combined immunodeficiency.
Abstract: Peripheral blood mononuclear cells (PBMC) from 14 foals with hereditary severe combined immunodeficiency (SCID) were studied to determine the extent of lymphocyte differentiation that occurs in this disorder. PBMC from all 14 horses had the morphologic characteristics of large granular lymphocytes (LGL). Cells from only one of 14 horses were responsive to phytolectin stimulation in a standard blastogenesis assay; however, PBMC from all 14 horses proliferated in continuous culture in the presence of partially purified interleukin 2. Furthermore, there were differences in the growth patterns of these cultured cells that correlated with their ability to respond to phytolectin stimulation. PBMC obtained from the 13 phytolectin-unresponsive foals survived in culture for only 4 to 5 wk, divided very slowly, developed large granules composed primarily of calcium phosphate, and accumulated high concentrations of histamine. In contrast, PBMC from the phytolectin-responsive SCID foal proliferated in continuous culture for over 100 days, divided as rapidly as normal equine PBMC under identical culture conditions, and did not accumulate granules or histamine. These observations indicate that lymphoid cell differentiation occurs in some horses with SCID even though the identity of the LGL is unresolved. Two possibilities are that LGL are products of a pathway separate from that of lymphocytes or that LGL are precursors of mature lymphocytes.
Publication Date: 1984-11-01 PubMed ID: 6207234
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- Journal Article
- Research Support
- Non-U.S. Gov't
- Research Support
- U.S. Gov't
- P.H.S.
Summary
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The research carries out a detailed study on how lymphocytes in horses with a deterring genetic disorder called Severe Combined Immunodeficiency (SCID) behave or change. The findings indicate that though these lymphocytes may not fully mature due to the disorder, some differentiation events occur.
Investigating Severe Combined Immunodeficiency (SCID) in Horses
- This study focuses on how the hereditary disorder, SCID, affects the differentiation of the lymphocytes in horses. This disorder is known to greatly impede the maturation of lymphocytes.
- The researchers study Peripheral blood mononuclear cells (PBMC) from 14 foals diagnosed with SCID. These foals offered an ample sample space for the study, allowing for better accuracy in the observations and findings.
Morphologic Characteristics of PBMCs
- All PBMCs sampled from the 14 foals exhibited the morphologic characteristics of large granular lymphocytes (LGL).
- However, there was a deviation observed, as cells from only one of the foals responded to phytolectin stimulation. This was determined using a standard blastogenesis assay. This shows that while the disorder may deter lymphocyte maturation, it may not entirely inhibit the responsiveness of cells to stimuli.
Growth Patterns and Phytolectin Responsiveness
- The growth patterns of the cultured cells varied, and they seemed to correlate with their ability to respond to phytolectin stimulation.
- PBMCs from 13 out of the 14 foals, those that didn’t respond to the phytolectin stimulation, survived in culture for only 4-5 weeks and divided very slowly. They also developed large granules composed mainly of calcium phosphate and accumulated high concentrations of histamine.
- Conversely, the PBMCs from the one phytolectin-responsive foal demonstrated different traits. They not only survived in continuous culture for over 100 days, but also divided as rapidly as a normal equine PBMC would under identical culture conditions. And they didn’t accumulate granules or histamine.
Lymphoid Cell Differentiation
- These observations from the study point towards the fact that despite SCID disorder obstructing lymphocyte maturation, lymphoid cell differentiation in horses does still occur. However, the type of differentiation that the large granular lymphocytes (LGLs) undergo remains undetermined.
- The researchers suggest two possibilities – either the LGLs are products of a separate pathway from that of lymphocytes or that they are precursors of mature lymphocytes. Further investigation is needed to firmly establish their identity.
Cite This Article
APA
Magnuson NS, Perryman LE, Wyatt CR, Ishizaka T, Mason PH, Namen AE, Banks KL, Magnuson JA.
(1984).
Continuous cultivation of equine lymphocytes: evidence for occasional T cell-like maturation events in horses with hereditary severe combined immunodeficiency.
J Immunol, 133(5), 2518-2524.
Publication
Researcher Affiliations
MeSH Terms
- Animals
- Calcium Phosphates / isolation & purification
- Cell Differentiation
- Cells, Cultured
- Cytoplasmic Granules / analysis
- Histamine Release
- Horses / immunology
- Immunologic Deficiency Syndromes / genetics
- Immunologic Deficiency Syndromes / immunology
- Immunologic Deficiency Syndromes / pathology
- Interleukin-2 / isolation & purification
- Interleukin-2 / physiology
- Lymphocyte Activation
- Phytohemagglutinins / pharmacology
- T-Lymphocytes / analysis
- T-Lymphocytes / immunology
- T-Lymphocytes / pathology
Grant Funding
- AI 10060 / NIAID NIH HHS
- CA 14496 / NCI NIH HHS
- HD 08886 / NICHD NIH HHS
Citations
This article has been cited 3 times.- Mealey RH, Kappmeyer LS, Ueti MW, Wagner B, Knowles DP. Protective effects of passively transferred merozoite-specific antibodies against Theileria equi in horses with severe combined immunodeficiency.. Clin Vaccine Immunol 2012 Jan;19(1):100-4.
- Mealey RH, Littke MH, Leib SR, Davis WC, McGuire TC. Failure of low-dose recombinant human IL-2 to support the survival of virus-specific CTL clones infused into severe combined immunodeficient foals: lack of correlation between in vitro activity and in vivo efficacy.. Vet Immunol Immunopathol 2008 Jan 15;121(1-2):8-22.
- Knowles DP Jr, Kappmeyer LS, Perryman LE. Specific immune responses are required to control parasitemia in Babesia equi infection.. Infect Immun 1994 May;62(5):1909-13.
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