Cooperating and Controlling Functions of Thymus-Derived Lymphocytes in Relation to Autoimmunity

Allison, A. C.; Denman, A. M.; Barnes, R. D.

doi:10.1016/s0140-6736(71)92306-3

Cited by 451 publications

(125 citation statements)

References 23 publications

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“…Secondly, they illustrate a simple mechanism for the maintenance of self-tolerance of the nude mouse to its serum proteins. Teleologically it would seem very desirable that B cells, as well as T cells (24), be self-tolerant since it is clear that ubiquitous substances such as endotoxin (25,26) and products from activated macrophages (18), which could in theory be stimulated by infection or inflammation, allow B cells to respond to thymus-dependent antigens in the absence of activated, specific T cells. Thus tolerance existing solely at the T cell level could be broken (27).…”

Section: Discussionmentioning

confidence: 99%

Induction of Immunological Tolerance to a Thymus-Dependent Antigen in the Absence of Thymus-Derived Cells

Schrader

1974

The Journal of Experimental Medicine

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Specific immunological unresponsiveness was induced using thymus-dependent antigens in congenitally athymic (nu/nu) mice, in which no T-cell function has been demonstrated. The tolerance was induced in vivo by the injection of 5–10 mg of either FGG or DNP-HGG. Spleen cells from treated mice were tested in vitro for the ability to mount thymus-independent immune responses against FGG in the presence of polymerized flagellin POL, and the DNP determinant conjugated to POL. A specific deficiency in either the in vitro anti-FGG or anti-DNP response was demonstrated, depending on the antigen used for treatment of the spleen cell donor. Athymic mice treated with FGG were also tested by in vivo challenge with FGG given with POL as an adjuvant and were found to be hyporesponsive. Unresponsiveness to in vitro challenge was established by 24 h after the in vivo injection of FGG. It was found that the injection of POL with the FGG prevented the development of unresponsiveness, but not if the POL was given 24 h or more after the FGG. The unresponsiveness could not be overcome by confrontation with allogeneic spleen cells from CBA mice, although the presence of allogeneic spleen cells had a large amplifying effect on the response of control spleen cells. These experiments demonstrate a mechanism for the tolerization of bone marrow-derived cells by thymus-dependent antigens in the absence of the thymus.

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Section: Discussionmentioning

confidence: 99%

Induction of Immunological Tolerance to a Thymus-Dependent Antigen in the Absence of Thymus-Derived Cells

Schrader

1974

The Journal of Experimental Medicine

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“…It is rapidly becoming clear that in certain antibody responses thymus-derived lymphocytes (T cells) are definitely endowed with a role to suppress responses of bone marrow-derived lymphocytes (B cells) to antigen (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). Such inhibitory effect of T cells led to a designation of "suppressor T cell" and is being recognized in large measure as an important regulatory device in various antibody responses.…”

mentioning

confidence: 99%

Selective Roles of Thymus-Derived Lymphocytes in the Antibody Response

Tada

Takemori

1974

The Journal of Experimental Medicine

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It is rapidly becoming clear that in certain antibody responses thymus-derived lymphocytes (T cells) are definitely endowed with a role to suppress responses of bone marrow-derived lymphocytes (B cells) to antigen (1-12). Such inhibitory effect of T cells led to a designation of "suppressor T cell" and is being recognized in large measure as an important regulatory device in various antibody responses. Some forms of immunological tolerance are also explained by the active suppression by T cells rather than the elimination of B-cell clones (12)(13)(14).The suppression by T cells has been shown to be mediated by both antigenspecific and nonspeclfiC mechanisms, while both pathways may be equally important for the regulation of antibody synthesis. Our previous studies (3) demonstrated that T cells primed with a carrier antigen suppressed an ongoing IgE antibody synthesis by B cells against a hapten coupled to the same carrier; thus this suppression appeared to be antigen-specific. The presence of a subcellular component of T cells that specifically suppresses the B-cell response was also reported (15).Our more recent studies on the specific suppression of IgM antibody response by T cells (11) showed another important fact, namely, that the T cell's suppressive effect on B cells varied depending on the time when the suppressor cells were given to the immunized recipients. The suppressor effect on the IgM antibody response was found to be more pronounced if the primed T cells were given to the recipients at a time when antibody-forming cells were starting to appear in their spleen rather than at the time of immunization. These observations suggest that the susceptibility of B cells to the suppressive effect of T cells is inherently different depending on the maturation stage of B cells and on the immunoglobulin classes which they are destined to produce. The present experiments were undertaken to study the mode and sites of action of suppressor T cells on antibody response in mice with special reference to the differential effect of T cells on B cells which produce IgM and IgG antibodies.

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“…Our interpretation follows the idea that during any pathological process (cancerous or not) involving reaction of the immune system, lymphocytes become sensitized to the self-antigens in parallel. For instance, the virus may be responsible for this deviation of immune reaction (Allison et al, 1971). It is relevant to this that one Coombs' positive patient and one patient grafted with lymphoid cells and undergoing the graft-versus-host reaction were positive in the HAT.…”

Section: Discussionmentioning

confidence: 97%

Agglutination of peripheral blood lymphocytes from cancer patients and not from healthy controls, with the F2A1 histone fraction

Sabolović¹,

Sabolovic²,

Moutte³

et al. 1975

Br J Cancer

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Summary.-A simple, rapid histone agglutination test (HAT) is described. It consists of incubation in microplates or in microtubes of blood lymphocytes isolated from cancer patients and patients with non-malignant diseases with microquantities of histone fraction F2AL. Positive reaction is shown by massive agglutination of lymphocytes of the patients tested (126 subjects): this test was positive in 76% of cases. All controls (59 subjects) were negative.

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Cooperating and Controlling Functions of Thymus-Derived Lymphocytes in Relation to Autoimmunity

Cited by 451 publications

References 23 publications

Induction of Immunological Tolerance to a Thymus-Dependent Antigen in the Absence of Thymus-Derived Cells

Induction of Immunological Tolerance to a Thymus-Dependent Antigen in the Absence of Thymus-Derived Cells

Selective Roles of Thymus-Derived Lymphocytes in the Antibody Response

Agglutination of peripheral blood lymphocytes from cancer patients and not from healthy controls, with the F2A1 histone fraction

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