Problems in the Physiology of Class I and Class II MHC Molecules, and of CD45

Fisher, Amanda G.; Goff, Lindsey K.; Lightstone, Liz; Marvel, Jacqueline; Mitchison, N A; Poirier, G; Stauss, Hans J.; Zamoyska, Rose

doi:10.1101/sqb.1989.054.01.078

Cited by 13 publications

(12 citation statements)

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“…It has been asked [17] [8,191 puts the protein at a level which would be expected to stimulate proliferation poorly but still elicit some tolerance. This is a marginal concentration, and suggests that at least as far as concerns F protein, no special mechanism of antigen presentation need be postulated within the thymus.…”

Section: Discussionmentioning

confidence: 99%

Tolerance of self induced in thymus organ culture

et al. 1992

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F liver protein occurs in serum at low concentration, and therefore induces tolerance of self only in T cells. T cells which mature in cultured thymus lobes in the absence of this protein become reactive towards it but can be prevented from doing so by exposure to the protein while in culture. The threshold of tolerance induction for this soluble antigen is estimated in this way at approximately 1 microgram/ml, which is slightly less than the threshold of response of primed T cells in a proliferation assay. Freshly isolated thymocytes do not display reactivity to self-F protein, indicating that T cells normally become tolerant while still within the thymus.

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Section: Discussionmentioning

confidence: 99%

Tolerance of self induced in thymus organ culture

et al. 1992

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“…This is not the case since the bulk of thymocytes selectively express only low-M, forms [13]. A plausible explanation to these apparently contradicting results has been offered by Mitchison and colleagues [14] (based on work in mouse) and Pilarsky and Deans [15] (based on work in humans), namely that Tcells in the thymus expressing CD45 low-M, isoforms, may be destined to intrathymic death. In this scheme, cells destined to enter the periphery express CD45 high-MI isoforms.…”

Section: Introductionmentioning

confidence: 90%

Expression of high molecular weight isoforms of CD45 by mouse thymic progenitor cells

Goff¹,

Larsson²,

Fisher³

1990

Eur J Immunol

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We have studied the expression of isoforms of CD45 (leukocyte common antigen, LCA) among T cell precursors using the organ culture system of Jenkinson et al. (Eur. J. Immunol. 1982. 12: 583). These experiments show that cells capable of recolonizing alymphoid embryonic thymic lobes in vitro can be detected in the thymus of fetal and adult mice and are enriched when thymocytes are depleted of cells bearing CD4 or CD8. These data are consistent with results from in vivo experiments of Fowlkes et al. (J. Exp. Med. 1985. 162: 802) indicating that T cell precursors lie within the double-negative (CD4-CD8-) compartment. No precursors were detected among the reciprocal populations of cells bearing CD4 and/or CD8 (single and double positives). Double-negative cell fractions were then divided on the basis of reactivity with monoclonal antibodies RA3-2C2 and RA3-3A1. These antibodies recognize the high molecular weight species of the LCA or, more accurately, a product defined by exon A of the CD45 gene. Recolonizing cells were found predominantly in the CD45RA+ (RA3-2C2 and RA3-3A1 reactive) fraction of double-negative thymocytes; CD45RA- enriched populations had increased efficiency of recolonization and CD45RA- depleted populations had decreased ability to recolonize as compared with the whole CD4-CD8- fraction. To clarify whether progenitors enriched in the CD45RA+ fraction were capable of giving rise to mature CD4+, CD8+ and CD4+ CD8+ cells, we analyzed the progeny of lobes seeded with CD4-CD8-CD45RA+ fractions. After 7-9 days in organ culture the proportion of CD4+, CD8+ or CD4+ CD8+ cells had increased to 35.2%, 18.6% and 23.7%, respectively (mean of five experiments), indicating that progenitors among the CD45RA+ population were indeed multipotent. These results suggest that the majority of T stem cells in the thymus are among thymocytes that express the CD45RA molecule, an hypothesis supported by our finding that removal of CD45RA-expressing cells (using complement and antibody) eliminated recolonizing capacity of thymic cell fractions.

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“…The most notable difference was that donor-specific restriction of mha-primed T h could be detected in the present system, although this had not been evident in the Thy-1 response. This presumably reflects presentation of the mha by class I1 MHC molecules of the cells used as antigen, either on these cells themselves [13], or perhaps after uptake onto host cells [14]. In contrast to the previous study with Thy-1 that used thymocytes as antigen, the spleen cells used here would have included class 11+ cells.…”

Section: Discussionmentioning

confidence: 95%

Latent help to and from H‐2 antigens

Mitchison

1992

Eur J Immunol

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An optimized system for probing allo-immunity to major histocompatibility complex (MHC) antigens by means of adoptive transfer is used to confirm and extend previous work showing that naturally occurring class I MHC antigens, while capable of inducing Th activity when presented in combination with other allo-antigens, fail to do so on their own. The Th activity which they do induce develops slowly, after repeated immunizations, and can properly be described as "latent". Latency, or "cripticity" as it is also termed, may help explain how autoimmune disease is initiated.

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Problems in the Physiology of Class I and Class II MHC Molecules, and of CD45

Cited by 13 publications

References 0 publications

Tolerance of self induced in thymus organ culture

Tolerance of self induced in thymus organ culture

Expression of high molecular weight isoforms of CD45 by mouse thymic progenitor cells

Latent help to and from H‐2 antigens

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