Cicatricial pemphigoid (CP) is a chronic autoimmune blistering disease affecting multiple mucous membranes derived from stratified squamous epithelium and occasionally the skin. CP has a wide spectrum of disease manifestations. Patients with oral pemphigoid (OP) have a benign self-limited disease in which pathological changes are restricted to the oral mucosa. On the other hand, patients with ocular cicatricial pemphigoid (OCP), a chronic condition marked with relapses and remissions, have ocular involvement and also perhaps involvement of other mucous membranes. AU clinical subsets are characterized by the presence of a similar antibasement zone autoantibody. The factors that determine the development of one form of CP or the other are not known. In a previous study, we described the asiation between OCP and the DQBI*0301 allele (P = 0.006). In this study, we have analyzed 22 Caucasian patients with OP and their family members for major histocompatibility complex DRB generic, DQA1, and DQBI allele associations by PCR-sequence-speciflc oligonucleotide probe hybridization. The results were compared to those obtained from 17 Cancasian patients with OCP and to control Caucasian alleles and haplotypes. The DQBI*0301 allele frequency was 38.6% in OP, 52.9% in OCP, and 17.8% in controls. Statistically siificant associations were detected between the DQB1*0301 allele and both OP (P = 0.0047) and OCP (P < 0.0001). In addition, DRB1*04 showed a statistically significant association (P = 0.005) with OCP when compared to controls. Analysis of major histocompatibility complex class H haplotypes showed sgfant statistical associations between both OCP and OP and the HLA-DRB1*04, DRB4*0101, DQA1*03, DQB1*0301 haplotype (P < 0.0001 and P = 0.0012, respectively). Our results indicate that DQBJ*0301 is a marker of both oral and ocular forms of CP. The analysis ofthe amino acid sequence oftheDQBl alleles present in both OP and OCP suggested that amino acid residues at position 57 and positions 71-77 may also be markers of CP.Cicatricial pemphigoid (CP) is an autoimmune blistering disease that involves multiple mucous membranes and occasionally the skin (1). The pathogenesis is attributed to the deposition in vivo of an anti-basement membrane antibody and complement leading to blister formation and subsequent progressive subepithelial fibrosis (2). CP has various clinical manifestations. When only the oral mucosa (oral pemphigoid, OP) is involved, the condition is usually benign and selflimited. In contrast, ocular CP (OCP) frequently involves other mucous membranes and has severe clinical manifestations and a chronic course requiring the use of high doses of corticosteroids and immunosuppressive agents to prevent blindness.In previous studies, we showed (3) an association between theDQBl *0301 allele and OCP (P < 0.003; relative risk = 9.6) when compared to a large population of healthy normal Caucasians. In that study, 19 out of 20 OCP patients carried DQ7 (DQBI*0301) (3). In addition, the presence ofHLA DQ7 was not due t...

Newly-hatched chickens, isogenic for the B locus, were treated with high doses of cyclophosphamide, either alone or in combination with surgical bursectomy. The cyclophosphamide treatment initially caused virtual absence of bursal lymphoid cells and, later, complete destruction of the normal bursal architecture. It also caused an initial decrease in the lymphoid population of the thymus. However, thymic morphology was completely restored in chickens that were 15 days old or older. The most striking features in the morphology of the spleen and of the other peripheral lymphoid tissues of cyclophosphamide-treated birds was the absence of germinal centers and of the plasma cell line. No clear morphological differences could be detected between birds that were treated with cyclophosphamide alone and those subjected to cyclophosphamide treatment in combination with surgical bursectomy. The immunological capacities of normal, cyclophosphamide-treated and cyclophosphamide-treated bursectomized chickens were evaluated, starting with 1-month-old birds. The experimental groups of animals lacked or were profoundly deficient in agglutinating antibody to B. abortus antigen and to sheep erythrocytes after primary and secondary stimulation, while the normal controls responded well. Profound deficiency of IgM and IgG, as measured by the radial diffusion technique, was also obtained in the majority of the birds treated with cyclophosphamide alone or in combination with surgical bursectomy in the newly-hatched period. No clear differences could be detected, in the lack of capacity to respond to antigenic stimulation or to form immunoglobulins, between the birds that were treated with cyclophosphamide alone and those treated with cyclophosphamide together with bursectomy. Cellular immunological functions of normal and of cyclophosphamide-treated chickens were evaluated with regard to capacity to reject allografts and to elicit the graft-versus-host reaction. Cyclophosphamide treatment in the newly-hatched period did not affect the cellular immunological capacities of 1-month-old or older birds. Thus, by using this experimental protocol, cyclophosphamide can be used to accomplish ‘chemical bursectomy’, resulting in a permanent, severe deficiency of the humoral immunological capacities more frequently than can be obtained with other presently available bursectomy methods, while leaving the cellular immunological capacities intact.

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We previously reported that gammadelta T cells mediate the expression of endogenous heat shock protein 65 (HSP65) in macrophages of mice with acquired resistance against infection with Toxoplasma gondii. We show here that HSP65 contributes to protective immunity by preventing apoptosis of infected macrophages. Macrophages of BALB/c mice, which readily acquired resistance to T. gondii infection with the low virulence Beverley strain, strongly expressed HSP65, and only a few of these macrophages underwent apoptosis. On the other hand, the BALB/c mice were susceptible to the infection with the high virulence RH strain of T. gondii; their macrophages did not express HSP65 and did undergo apoptosis. Mice depleted of gammadelta T cells using a mAb specific for TCR-gammadelta became highly susceptible to infection even with the Beverley strain. In these mice, HSP65 expression was markedly suppressed, and their infected macrophages died via apoptosis. Apoptosis was induced in cultured macrophages or macrophage cell lines after infection in vitro with the RH strain, whereas apoptosis was prevented when HSP65 was induced in these cells, before infection, by activation with IFN-gamma and TNF-alpha. However, apoptosis associated with infection by T. gondii RH strain was not prevented when HSP65 synthesis was inhibited by introducing an antisense oligonucleotide for this protein into the cells before activation with IFN-gamma plus TNF-alpha. Thus, HSP65 appears to contribute to immunity by preventing the apoptosis of infected macrophages, and the high virulence Toxoplasma appears to have mechanisms that allow these organisms to evade the host defense system by interfering with HSP65 expression.