Evidence for an immunoglobulin-dependent antigen-specific helper T cell.

Janeway, Charles A.; Murgita, Robert A.; Weinbaum, Fredric I.; Asofsky, Richard; Wigzell, Hans

doi:10.1073/pnas.74.10.4582

Cited by 124 publications

(60 citation statements)

References 17 publications

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“…Several studies have shown that the expression of germ-line idiotypes may be only dominant early in an antibody response (37,38). Furthermore, experiments using helper T cells from normal and anti-#-treated mice demonstrate that the Ig-dependent T cells were only active early during an anti-DNP response (9). Taken together, these data lend support to the concept that preferential activation of frequently represented B cells may be a result of the ThId cell set.…”

Section: Discussionsupporting

confidence: 69%

Antigen-specific helper T cells required for dominant production of an idiotype (THId) are not under immune response (Ir) gene control.

Bottomly¹,

Maurer²

1980

The Journal of Experimental Medicine

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Responder and nonresponder mice primed with poly-(L-glutamic acid,L-lysine,L-phenylalanine) (GLPhe), the response to which is under the control of immune response (Ir) genes, were used as a source of both types of helper T cells required for a T15 idiotype dominated T-dependent anti-phosphorylcholine (PC) response. It was found that the activity of one of the helper T cells needed for an anti-PC response was under major histocompatibility complex (MHC)-linked Ir gene control, and only GLPhe-primed responder mice could be used as a source of these cells. These T cells (ThMHC) whose presence is required for in vivo T-B collaboration are found in normal and anti-mu-treated mice, and their activity depends on the hapten being physically linked to the carrier molecule. By contrast, the activity of the second helper T cell (ThId) required for a T15-dominated anti-PC response was present in both GLPhe-primed responder and nonresponder mice. The ThId cell set that is missing or deficient in anti-mu treated mice can be restored by the addition of T cells from normal, carrier-primed donors and restimulating with the priming carrier. When T cells from GLPhe-primed donors are used as a source of ThId cells, both responder and nonresponder donors provide helper cells capable of inducing syngeneic B cells to produce a T15 dominated anti-Pc response. These results are interpreted to suggest that idiotype recognizing helper T cells (ThId) recognize antigen independent of known Ir gene products.

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Section: Discussionsupporting

confidence: 69%

Antigen-specific helper T cells required for dominant production of an idiotype (THId) are not under immune response (Ir) gene control.

Bottomly¹,

Maurer²

1980

The Journal of Experimental Medicine

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“…Furthermore, adequate T-cell priming for a hapten does not require the presence of circulating antibody; this result argues against the existence of an Igdependent, antigen-specific helper T-cell population (16). Passively acquired antibody cannot function as the T-cell receptor in this system, because male Fx hybrids with the immune defect are unable to mount antibody responses to PC and lack detectable anti-PC antibodies in their serum (.5).…”

Section: Resultsmentioning

confidence: 95%

Phosphorylcholine-specific helper T cells in mice with an X-linked defect of antibody production to the same hapten.

Kaplan¹,

Quintáns²

1979

The Journal of Experimental Medicine

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F1 male mice with the CBA/N X-linked defect that are unable to produce plaque-forming cell responses to phosphorylcholine (PC) provide normal PC-specific helper T-cell activity when compared to F1 female littermates. Inhibition of helper activity with anti-idiotypic antiserum indicates that PC-specific T cells from both NBF1 female and male mice possess predominantly BALB/c myeloma protein HOPC-8 idiotypic determinants. Therefore, the CBA/N defect cannot be explained as a deletion of genes coding for V-region anti-PC specificities. The demonstration of helper activity in NBF1 male mice, which occurs in the absence of anti-PC antibody synthesis, also demonstrates the endogenous origin of the T-cell receptor.

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“…This may be due to the differential ability of B cells and other APCs to determine the class of CD4 T-cell response (41,42) and related to the difficulty in inducing "'anergy" in Th2-type T cells (43). Such selective T/B-cell interactions may also account for the extensive evidence produced in the past for the B-cell dependence of T-cell repertoires (44)(45)(46). In this view, self SAgs would play fundamental roles in regulating structural and functional T-lymphocyte repertoires, but the respective deletions, rather than constituting the bases of self tolerance, should instead be taken as a particular aspect ofrepertoire selection.…”

Section: Methodsmentioning

confidence: 96%

Transplantation tolerance is unrelated to superantigen-dependent deletion and anergy.

Salaün

Bandeira

Khazaal

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

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C57BL/6 (B6; I-E-, Mls-2b) nude mice, reconstituted at birth with thymic epithelium (TE) from BALB/c (BA; I-E+, Mls-2') day 10 embryos (E10), permanently accepted BALB/c skin, when grafted as adults. T-cell receptor repertoire analyses in the periphery of these mice revealed no difference in frequencies of I-E/superantigen-reactive T-cell receptor Vp families, as compared to chimeras constructed with syngeneic B6 E10 TE. T lymphocytes bearing Vp3, Vp5, and Vp11 T-cell receptors, from either allogeneic or syngeneic TE chimeras, responded equally well to in vitro receptordependent stimulation. Similar results were obtained with nude mice reconstituted at birth with E14 thymuses, already colonized by hemopoietic cells. These observations indicate that neither TE cells nor the progenies of hemopoletic precursors that colonize the thymus up to E14 express or functionally present the superantigens addressed here; it follows that tolerance to skin grafts and superantigen-related T-cell deletions are unrelated phenomena.Tolerance to self antigens is acquired during development through complex mechanisms that operate in the thymus and at the periphery. It is established that thymic epithelium (TE) is capable of inducing full tolerance to different tissues. Thus, chickens grafted with quail TE in embryonic life permanently accept wings, skin, and bursa of Fabricius from the donor species (1, 2). Tolerance to fully allogeneic skin grafts has also been obtained in amphibian embryos, by fusing the entire rear part of the body, containing the hemopoietic anlagen, to the anterior end of an allogeneic embryo, containing the TE primordia (3). In mice, allogeneic TE removed at 10 days of gestation (E10), when it is still devoid of hemopoietic precursors (4-6), induces long-lasting tolerance to skin, cartilage, and heart transplants, if grafted into newborn nude recipients (ref. 7; unpublished data).Clonal inactivation, through deletion or anergy, is currently considered the main mechanism operating in tolerance induction (reviewed in ref. 8), but the requirement for negative selection in natural tissue tolerance is yet to be established (see ref. 9 for discussion). Much support for that notion comes from the analysis of V13 T-cell receptor (TCR) families "recognizing" endogenous (10, 11) or external superantigens (SAgs) (12). As evidence exists against expression of SAgs by TE, notably Mls-1 (13-15) and I-E-associated Etc-i (16), it seemed important to investigate, in TE chimeras, the correlation between transplantation tolerance and deletion or anergy of SAg-related T cells. We show here that tolerant TE chimeras contain control frequencies of functionally competent T cells directed at SAgs from the donor strain. These results indicate that TE does not express, functionally at least, the corresponding SAgs, a conclusion that also applies to the first wave of hemopoietic thymic accessory cells colonizing the fetal thymus up to E14. MATERIAL AND METHODSMice. Mice were bred in our own facilities. Grafts of E10 (24-28 somite...

show abstract

Evidence for an immunoglobulin-dependent antigen-specific helper T cell.

Cited by 124 publications

References 17 publications

Antigen-specific helper T cells required for dominant production of an idiotype (THId) are not under immune response (Ir) gene control.

Antigen-specific helper T cells required for dominant production of an idiotype (THId) are not under immune response (Ir) gene control.

Phosphorylcholine-specific helper T cells in mice with an X-linked defect of antibody production to the same hapten.

Transplantation tolerance is unrelated to superantigen-dependent deletion and anergy.

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