T lymphocyte lines producing or vaccinating against autoimmune encephalomyelitis (EAE). Functional activation induces peanut agglutinin receptors and accumulation in the brain and thymus of line cells

Naparstek, Yaakov; Ben‐Nun, Avraham; Holoshitz, Joseph; Reshef, Tamara; Frenkel, A.; Rosenberg, Mireille; Cohen, Irun R.

doi:10.1002/eji.1830130513

Cited by 133 publications

(36 citation statements)

References 20 publications

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“…The present finding that T blasts remain in the thymus for at least 4 wk with no decline in their numbers is thus highly surprising . Nevertheless, the data are in accord with reports that T cells stimulated with myelin basic protein (3,4) or minor histocompatibility antigens (21) can enter the thymus and remain there for at least 2 mo post-transfer. Since the cells recovered from the thymus in these latter studies expressed effector activity only after reactivation with antigen in vitro, blast cells entering the thymus presumably revert rapidly to resting cells.…”

Section: Migration Of T Blasts To the Thymussupporting

confidence: 90%

“…As discussed earlier (see Introduction), passive transfer of self antigens into the thymus might serve to promote self tolerance induction . It is notable that autoreactive T cells can return to the thymus after activation in the periphery (3,4). Such homing could be a device to inhibit the further production of T cells with similar self specificity; the blasts might carry MHC/self antigen complexes (see references 22 and 23) into the thymus and display these complexes to newly formed T cells in tolerogenic form.…”

Section: Migration Of T Blasts To the Thymusmentioning

confidence: 99%

“…This notion rests on the assumption that lymphocyte traffic from the thymus is strictly unidirectional . However, there are a number of reports that T cell lines or mature lymphocytes harvested from the secondary lymphoid organs are able to localize in the thymus in appreciable numbers after intravenous injection (3)(4)(5)(6) . These cells localize largely in the medulla .…”

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confidence: 99%

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Reentry of T cells to the adult thymus is restricted to activated T cells.

Agus

Surh

Sprent

1991

The Journal of Experimental Medicine

248

165

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SummaryTo seek information on the capacity of mature T cells to migrate to the thymus, mice were injected with Thy-l-marked populations enriched for resting T cells or T blast cells ; localization of the donor cells in the host thymus was assessed by staining cryostat sections of thymus and by FACS® analysis of cell suspensions . With injection of purified resting T cells, thymic homing was extremely limited, even with injection of large doses of cells. By contrast, in vivo generated T blast cells migrated to the thymus in substantial numbers . Thymic homing by T blasts was >50-fold more efficient than with resting T cells . Blast cells localized largely in the medulla and remained in the thymus for at least 1 mo post-transfer. Interestingly, localization of T blasts in the thymus was 10-fold higher in irradiated hosts than normal hosts . Thymic homing was especially prominent in mice injected with T blasts incubated in vitro with the DNA precursor, 125 I-5-iodo-2'deoxyuridine ( 125IDUR); with transfer of 125IDURlabeled blasts to irradiated hosts, up to 5% of the injected counts localized in the host thymus. These data suggest that thymic homing by T blasts might be largely restricted to cells in S phase. The physiological significance of blast cell entry to the thymus is unclear. The possibility that these cells participate in intrathymic tolerance induction is discussed.

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Section: Migration Of T Blasts To the Thymussupporting

confidence: 90%

Section: Migration Of T Blasts To the Thymusmentioning

confidence: 99%

mentioning

confidence: 99%

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Reentry of T cells to the adult thymus is restricted to activated T cells.

Agus

Surh

Sprent

1991

The Journal of Experimental Medicine

248

165

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“…Initially, radioisotope-labeled (14,15) and, recently, GFP-transduced (4, 16) encephalitogenic T cells were injected into naive animals to induce adoptively transferred EAE, and the markers were traced in lymphoid and target organs during the disease course. Fluegel et al (4) demonstrated that the transferred cells reduce the expression of activation molecules, such as MHC class II Ags, OX40, and IL2Rs, and re-express them after entry into the CNS.…”

Section: Discussionmentioning

confidence: 99%

Tracking of Vβ8.2-Positive Encephalitogenic T Cells by Complementarity-Determining Region 3 Spectratyping and Subsequent Southern Blot Hybridization in Lewis Rats after Neuroantigen Sensitization

Sakuma

Kohyama

Jee

et al. 2004

The Journal of Immunology

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Pathogenic T cells in organ-specific autoimmune diseases use a limited number of TCR α- and β-chains. In experimental autoimmune encephalomyelitis (EAE) induced in Lewis rats by immunization with myelin basic protein, encephalitogenic T cells mainly use Vβ8.2 TCR and clonal expansion of the Vβ8.2 spectratype containing the EAE-specific complementarity-determining region 3 (CDR3) sequence, DSSYEQYFGPG, is found in the spinal cord throughout the course of clinical EAE. In the present study we performed temporal and spatial analyses of Vβ8.2 spectratype expansion by CDR3 spectratyping and subsequent DNA hybridization with a probe specific for the encephalitogenic CDR3 sequence to elucidate the kinetics of encephalitogenic T cells during the induction phase after neuroantigen sensitization. It was demonstrated that Vβ8.2 spectratype expansion and/or the positive signal in Southern blot were first detected in the regional lymph nodes as early as day 3 postimmunization and was disseminated over the lymphoid organs by day 6. Because perfusion of immunized rats with PBS erased the positive signals on day 3 postimmunization, the majority of Vβ8.2-positive encephalitogenic T cells at the very early stage would reside within the lymphatic or blood vessels. Furthermore, removal of the draining lymph node 1, 3, and 6 days after immunization in the foot pad did not ameliorate clinical EAE. These findings strongly suggest that encephalitogenic T cells disseminate throughout the whole body very rapidly after sensitization. Analysis of pathogenic T cells at the clonal level provides useful information for designing effective immunotherapy.

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“…Line A2 reactive to MT was isolated and maintained as described (3 (6) or against experimental autoimmune thyroiditis (EAT) (7). The lymphoblasts were collected, separated from residual accessory cells and from cellular debris by density gradients in some experiments (see Table I), washed twice in PBS, and injected in 1 ml of PBS into the tail vein of nonirradiated Lewis rats.…”

Section: Methodsmentioning

confidence: 99%

Role of the thymus in induction and transfer of vaccination against adjuvant arthritis with a T lymphocyte line in rats.

Holoshitz¹,

Matitiau²,

Cohen³

1985

J. Clin. Invest.

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Adjuvant arthritis is an experimental disease of rats induced by immunization to antigens of Mycobacterium tuberculosis. Our observation that arthritis could be induced in irradiated rats by the A2 line of T lymphocytes in the absence of mycobacterial antigens suggested that adjuvant arthritis is an autoimmune disease. Moreover, the A2 line could be used to vaccinate unirradiated rats against the subsequent induction of adjuvant arthritis by active immunization to Mycobacteia. In the present study we found that thymus cells obtained from A2 vaccinated rats could transfer resistance to adjuvant arthritis to naive rats. This indicates that the mechanism of resistance induced by A2 vaccination is probably immunological and involves thymus-derived lymphocytes.

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T lymphocyte lines producing or vaccinating against autoimmune encephalomyelitis (EAE). Functional activation induces peanut agglutinin receptors and accumulation in the brain and thymus of line cells

Cited by 133 publications

References 20 publications

Reentry of T cells to the adult thymus is restricted to activated T cells.

Reentry of T cells to the adult thymus is restricted to activated T cells.

Tracking of Vβ8.2-Positive Encephalitogenic T Cells by Complementarity-Determining Region 3 Spectratyping and Subsequent Southern Blot Hybridization in Lewis Rats after Neuroantigen Sensitization

Role of the thymus in induction and transfer of vaccination against adjuvant arthritis with a T lymphocyte line in rats.

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