The Smyth line chicken (SL), an avian model for autoimmune vitiligo, is characterized by a postnatal loss of melanin pigmentation in feathers and the choroid of the eye. Earlier studies supported a hypothesis that an inherent pigment cell defect is necessary for the amelanosis which is the consequence of the selective destruction of melanocytes by the immune system. Data collected during the last decade has demonstrated that the MHC plays a major role in the development and severity of the SL vitiligo. The major objective of this study was to determine the factors contributing to the variable expression of the disease in the SL102 subline, selected by serotyping to be homozygous for the 102 MHC haplotype. The homogeneity of the MHC loci among SL102 and BL (parental control) birds was evaluated by serological, mixed lymphocyte response (MLR) and restriction fragment length polymorphism (RFLP) techniques. The results of these analyses were then studied in respect to their effects on the variation in incidence and severity of autoimmune vitiligo. All SL102 birds used in these studies appeared to carry the same, or nearly identical Ea-B haplotype as determined by serology as well as by MLR. Surprisingly, only 15 out of 22 BL birds were homozygous for Ea-B102, possibly due to a previous pedigreeing error. RFLP genotype assignment based on 4 different restriction enzymes and MHC class I and class II probes did not appear to have any influence on the incidence of vitiligo. No polymorphisms were found among SL102 birds using class II probe, while 2 RFLP genotypes were revealed with the class I probe. One of these loci was shown (P $<$.05) to be associated with the severity of the vitiligo. Peripheral blood lymphocytes obtained from the serologically haplotype matched SL, BL and an unrelated control (LBL) birds were analyzed for their mitogenic responses as well as their lymphocyte subset populations. SL102 birds had a higher proportion of CD4+ and CD8+ T-cells and a lower proportion of TCR1+ T-cells; but, they were also the poorer responder to a T-cell mitogen, ConA. One of the variant B-F RFLP polymorphisms was associated with a low ConA response, although these birds had a higher proportion of CD8+ T-cells than controls. From this study it is hypothesized that MHC class II locus is involved in the incidence of autoimmune vitiligo where as the severity of the disease is associated with MHC class I genes. The variation in mitogenic response and lymphocyte subset populations are possibly associated with subline differences that may not be MHC-related.
| Identifer | oai:union.ndltd.org:UMASS/oai:scholarworks.umass.edu:dissertations-8811 |
| Date | 01 January 1994 |
| Creators | Lakshmanan, Nalla Kannu |
| Publisher | ScholarWorks@UMass Amherst |
| Source Sets | University of Massachusetts, Amherst |
| Language | English |
| Detected Language | English |
| Type | text |
| Source | Doctoral Dissertations Available from Proquest |
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