A quantitative model of autoimmune disease and T-cell vaccination: does more mean less?

Modelling T-cell-Mediated Suppression Dependent on Interactions in Multicellular Conjugates

“…No mathematical model has been developed to study the quantitative implications of such interactions on cell population dynamics. Available mathematical models of T-cell-mediated suppression have addressed the possibility that this suppression is mediated by soluble factors, as in the class regulation models of Fishman & Perelson (1994) and others, or they have addressed the possibility of suppression mediated by a direct cell contact between a suppressor clone and an antigen-speci"c responder clone, as in classical idiotypic network models (Cohen & Atlan, 1989;Perelson, 1989) or in the more recent T cell vaccination models (Borghans & De Boer, 1995;Segel et al, 1995). Here we report the development and analysis of a mathematical model, in which the regulatory 232 interactions between T cells take place only in multicellular conjugates with their APC.…”

Indirect Effects of Oral Tolerance Cannot be Ascribed to Bystander Suppression

“…There is recent evidence for lifelong stabilities in natural auto-reactive immunoglobulin patterns [41][42][43] and for marked maternal effects on the creation of these patterns [44]. Furthermore, there is compelling evidence that interventions designed to alter patterns of auto-reactivity, such as immunization with synthetic peptides mimicking paratopes and idiotopes [45], or with T cell clones [46], may prevent or even revert experimental autoimmune diseases or the lesions of disease-prone mouse strains. We have preliminary evidence that the indirect effects of parenteral exposure to low doses (10 mg) of ovalbumin in B6D2F1 mice receiving spleen cells from Ova orally tolerant C57BL/6 mice may significantly prolong the life, and ameliorate the symptoms, of graft-versus-host disease [29].…”

Mathematical model for alopecia areata

“…The CD4 þ T-cell population declines as CD4 þ T-cells undergo natural death ðÀd T4 T4Þ or die because of inter-cell competition ðÀκ T4 ðT4Þ 2 Þ (Borghans et al, 1998;Yates et al, 2000;Segel et al, 1995). As noted earlier, AA-affected hair follicles experience hair cycle disruption: premature termination of anagen and induction of catagen.…”

“…The clonal expansion of effector CD8 þ T-cells/ NKG2D þ cells is promoted by co-stimuatory and cell division signals provided by CD4 þ T-cells, and proliferation is hindered by immune privilege guardians p T8 γT4T8 1 þ σIPG . The CD8 þ T-cell/NKG2D þ cell population decreases due to natural cell death ðÀd T8 T8Þ, and if the population size is significantly large, there is also death associated with competition among CD8 þ T-cells/NKG2D þ cells ðÀκ T8 ðT8Þ 2 Þ (Borghans et al, 1998;Yates et al, 2000;Segel et al, 1995). Autoreactive CD4 þ T-cells migrate to hair follicles, and activation of these cells is stimulated by IFN-γ and inhibited by immune The immune privilege agents also 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 .…”