An immunodeficiency in Fell ponies: a preliminary study into cellular responses

Abstract

A putative immunodeficiency, causing mortality in UK Fell pony foals (Fell pony syndrome), was studied in affected foals and compared with healthy, age-matched foals. Differential cell counts of peripheral blood indicated that the syndrome foals were lymphopenic (P<0.05). Flow cytometric analysis of circulating leucocytes showed a reduced MHC II e x p ression (P<0.01) on lymphocytes but not on polymorphonuclear cells in affected foals. There were no changes in the percentages of CD4 + or CD8 + T cells. There was an increased (P<0.05) expression of CD11a/18 by the lymphocytes of the syndrome foals, compared to the control foals, which is probably a response to systemic bacterial infections. The syndrome foals' lymphocytes responded to mitogens (PHA, ConA, PWM) at normal levels. The data do not conform to any known immunodeficiencies identified in any other species. Furt h e r analyses will be re q u i re d , particularly on bone marrow function.

Fell Pony Syndrome: Characterization of Developmental Hematopoiesis Failure and Associated Gene Expression Profiles

“…CD4 ϩ and CD8 ϩ T cells are also imperative in the control of adenovirus infection (20,64,65). Our study did not document a failure in the expression of MHC class II molecules in lymphocytes of FPS-affected foals, reported in other studies; yet, such finding would further support abnormal lymphocyte development (3,23,43). Further studies focused on T cell differentiation and function in FPS-affected foals are necessary to confirm the involvement of yet another cell lineage in this syndrome, the T cells.…”

“…A second clinical report with similar findings followed (57). Bell and coworkers (3) described that FPS-affected foals had fewer total lymphocytes than healthy foals, and the distribution of CD4 ϩ and CD8 ϩ T lymphocytes appeared normal. The expression of major histocompatibility complex class II (MHC class II) molecule was decreased in peripheral blood lymphocytes in comparison to that in healthy foals.…”

Identification of a Mutation Associated with Fatal Foal Immunodeficiency Syndrome in the Fell and Dales Pony

“…Further investigation into the physiological consequences of this mutation will then also be possible. In particular, it will be important to identify how the mutation leads to profound anemia and B-lymphopenia whilst neutrophils and T-cell numbers (including CD4/CD8 ratio) and function (responses to mitogens PHA and Con A) appear normal [4]. Importantly, it must be investigated whether there is a defect in T-cell function that is currently undetected or whether the antigen presenting function of B-cells is so suppressed that the T-cells cannot respond.…”

“…Despite an initial response to treatment, the infections persist and were shown to be due to a primary B-cell deficiency [2] associated with reduced antibody production, with tested immunoglobulin isotypes including IgM, IgGa, IgGb and IgG(T) being significantly reduced [3]. Paradoxically, circulating T-lymphocyte numbers are normal [4]. The reduced antibody levels in affected foals are consistent with an inability to generate an adaptive immune response, resulting in immunodeficiency once colostrum-derived immunoglobulin levels decrease at 3–6 weeks of age.…”

“…The underlying lesion was found to be a 5 base-pair deletion in the gene coding DNA-dependent kinase, catalytic subunit DNA-PK CS [8], a protein involved in V(D)J recombination required for adaptive immunity [9]. Like FIS foals, SCID foals have a markedly reduced thymus and have reduced numbers of germinal centers in secondary lymphoid organs [10]; unlike SCID foals however, FIS foals have apparently normal numbers of circulating T-cells [4]. Primary aggamaglobinemia is rare in horses and comprises of a complete absence of immunoglobulin and reduced peripheral B-lymphocyte levels, with normal T-lymphocyte activity [11].…”