Canine X-linked severe combined immunodeficiency

Peter J. Felsburg, Brian J. Hartnett, Paula S. Henthorn, Peter F Moore, Steven Krakowka, Hans D. Ochs

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Canine X-linked severe combined immunodeficiency (XSCID) is due to mutations in the common gamma (γc) subunit of the IL-2, IL-4, IL-7, IL-9 and IL-15 receptors. The most striking clinical feature is a failure to thrive or 'stunted' growth. Recurrent or chronic infections begin at the time of decline of maternal antibody, usually between six and eight weeks of age. Affected dogs rarely survive past three to four months of age. The major pathologic feature of canine XSCID is a small, dysplastic thymus. Grossly identifiable lymph nodes, tonsils, and Peyer's patches are absent in XSCID dogs. During the neonatal period, XSCID dogs have few, if any, peripheral T cells and increased number of peripheral B cells. Some XSCID dogs do develop phenotypically mature, nonfunctional T cells with age, however, the absolute number of peripheral T cells remain significantly decreased compared to age- matched normal dogs. An interesting finding is that as soon as T cells begin to appear in XSCID dogs they rapidly switch from a CD45RA+ (naive) phenotype to a CD45RA- (activated or memory phenotype). One of the characteristic findings in XSCID dogs is an absent or markedly depressed blastogenic response of T cells in response to stimulation through the T cell receptor and when the necessary second messengers for cellular proliferation are directly provided that by-pass signals delivered through ligand-receptor interaction. The proliferative defect is due to the inability of T cells to express a functional IL-2 receptor. Canine XSCID B cells do not proliferate following stimulation with T cell-dependent B cell mitogens, however, they proliferate normally in response to T cell-independent B cell mitogens. Canine XSCID B cells are capable of producing IgM but are incapable of class- switching to IgG antibody production following immunization with the T cell- dependent neoantigen, bacteriophage ΦX174. The number of thymocytes in the XSCID thymus is ≃0.3% of the thymocytes present in the thymus of age-matched normal dogs. The proportion of CD4-CD8- thymocytes in XSCID dogs is increased 3.5-fold and the CD4+CD8+ population is decreased 2.3-fold. These findings demonstrate that (1) a functional γc is required for normal B and T cell function, (2) early T cell development is highly dependent upon a functional γc, and (3) B cell development can occur through a γc- independent pathway.

Original languageEnglish (US)
Pages (from-to)127-135
Number of pages9
JournalVeterinary Immunology and Immunopathology
Volume69
Issue number2-4
DOIs
StatePublished - Aug 2 1999

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X-Linked Combined Immunodeficiency Diseases
severe combined immunodeficiency
Canidae
T-lymphocytes
T-Lymphocytes
Dogs
dogs
B-Lymphocytes
B-lymphocytes
Thymocytes
thymocytes
Thymus Gland
receptors
Mitogens
interleukin-2
Interleukin-15 Receptors
Interleukin-9
Growth Disorders
Immunoglobulin Class Switching
interleukin-9

Keywords

  • B cells
  • Canine
  • Common gamma chain
  • Immunodeficiency
  • T cells

ASJC Scopus subject areas

  • Immunology
  • veterinary(all)

Cite this

Felsburg, P. J., Hartnett, B. J., Henthorn, P. S., Moore, P. F., Krakowka, S., & D. Ochs, H. (1999). Canine X-linked severe combined immunodeficiency. Veterinary Immunology and Immunopathology, 69(2-4), 127-135. https://doi.org/10.1016/S0165-2427(99)00049-5

Canine X-linked severe combined immunodeficiency. / Felsburg, Peter J.; Hartnett, Brian J.; Henthorn, Paula S.; Moore, Peter F; Krakowka, Steven; D. Ochs, Hans.

In: Veterinary Immunology and Immunopathology, Vol. 69, No. 2-4, 02.08.1999, p. 127-135.

Research output: Contribution to journalArticle

Felsburg, PJ, Hartnett, BJ, Henthorn, PS, Moore, PF, Krakowka, S & D. Ochs, H 1999, 'Canine X-linked severe combined immunodeficiency', Veterinary Immunology and Immunopathology, vol. 69, no. 2-4, pp. 127-135. https://doi.org/10.1016/S0165-2427(99)00049-5
Felsburg, Peter J. ; Hartnett, Brian J. ; Henthorn, Paula S. ; Moore, Peter F ; Krakowka, Steven ; D. Ochs, Hans. / Canine X-linked severe combined immunodeficiency. In: Veterinary Immunology and Immunopathology. 1999 ; Vol. 69, No. 2-4. pp. 127-135.
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