Partial characterization and purification of murine T cell-replacing factor, TRF—II

Hübner, L.; Müller, G; Schimpl, Anneliese; Wecker, Eberhard

doi:10.1016/0161-5890(78)90023-8

Cited by 37 publications

(6 citation statements)

References 7 publications

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“…BHF-containing supernatants were derived from different cloned TH lines, from EL-4 thymoma cells (27), or from secondary MLC, and none of these BHF preparations had the capacity to bypass the specific Tn or LPS signals. Moreover, it is shown that BHF acts on B cell proliferation but is not required for differentiation into PFC, in contrast to widely accepted current hypothesis (3,8,(11)(12)(13).…”

contrasting

confidence: 62%

“…In contrast, this shows that BHF was required for significant clonal expansion to occur. Whether a differentiation enhancing component was also present in the BHF (3,(8)(9)(10)(11)(12)(13) and whether such a component is in fact required is not known because the LPS-signal or the specific TH signal (in the absence of which BHF activity could not be tested) induced differentiation by themselves.…”

Section: Effects Of Bhf Derived From Long-term T Cell Clones Two Difmentioning

confidence: 99%

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Requirement for three signals in "T-independent" (lipopolysaccharide-induced) as well as in T-dependent B cell responses.

Zubler¹,

Glasebrook²

1982

The Journal of Experimental Medicine

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It has recently been reported (1-3) that at least three different activation signals are required by resting B lymphocytes to generate clones of antibody-secreting cells during a T helper cell (Tn)Ldependent humoral immune response: one signal is generated when B cells "see" antigen, another one when the TH recognize major histocompatibility complex (MHC) (I region) determinants on the B cell. These two early signals are apparently required to render the B cell responsive to a third signal provided by T cell-derived nonspecific helper factor(s) for B cell responses (BHF). Thus, TH provide two different types of B cell activation signals, one MHC-carrierspecific and one nonspecific (1-6). But it is still not clear whether an antigen (hapten)-B cell interaction generates by itself an activation signal or serves only to focus haptenlinked carrier determinants (and thus T help) onto the B cell (4, 7). In addition, it is not clear at the present time whether different factors (interleukins) are involved in B cell proliferation vs. differentiation (8-15) and whether the MHC-carrier-specific Tnsignal can be mediated by soluble T cell products (16-18). There is still conflicting evidence concerning the capacity of combinations of interleukins, e.g., concanavalin A (Con A) supernatants or secondary mixed leukocyte culture supernatants (MLC SN), to entirely substitute for Tn in T cell-depleted B cell cultures (8-15, 19, 20).If there is a requirement for at [east three signals in Tn-dependent B cell responses, one may also have to reconsider the hypothesis that a mitogen such as bacterial lipopolysaccharide (LPS) can bypass all three signals and by itself induce a full B cell response (3,21). Different authors have to some extent observed synergistic effects between LPS and antigen (22, 23) or T help (24, 25) or both (26) but not a strict requirement for three signals. A major problem in the study of B cell activation, in particular concerning the role of LPS or the capacity of BHF to act as T-replacing factor, resides in the fact that B cell populations used for such studies still contain T cells that can themselves provide signals, especially in high density cultures.

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contrasting

confidence: 62%

Section: Effects Of Bhf Derived From Long-term T Cell Clones Two Difmentioning

confidence: 99%

Requirement for three signals in "T-independent" (lipopolysaccharide-induced) as well as in T-dependent B cell responses.

Zubler¹,

Glasebrook²

1982

The Journal of Experimental Medicine

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“…Farrar et al (22), Farrar and Koopman (23), and Simon et al (24) have shown that T-cell mitogenic factor (TMF) stimulates thymocyte proliferation and provides helper activity for both antibody responses and cytotoxic T-cell responses in culture. Both TCGF as described in this communication and TMF (22) appear to be indistinguishable from the thymocyte-stimulated factor described by Chen and DiSabato (25), the cytotoxic helper factor of Shaw et al (19,20), and several other nonspecific helper factors (26)(27)(28)(29)(30). The lymphocyte-activating factors (LAF) secreted by macrophages, or tumor cell lines that retain macrophage-like functions, appear to be a separate class of factors (31)(32)(33)(34) as they are associated with molecules having a moi wt of 15,000.…”

Section: Molecular Properties Of Lymphokinessupporting

confidence: 49%

Biochemical and biological characterization of lymphocyte regulatory molecules. I. Purification of a class of murine lymphokines.

Watson¹,

Gillis²,

Marbrook³

et al. 1979

The Journal of Experimental Medicine

281

114

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Murine spleen cells activated by concanavalin A (Con A) in culture produce a class of lymphokine molecules which possess biological activity in a number of lymphocyte response assays. Lymphokines with a mol wt of 30,000, as estimated from gel filtration studies, can be resolved into two components which differ by charge, with isoelectric point (pI) values of 4.3 and 4.9, respectively. Both components stimulate (a) the growth of established T-cell lines in culture, (b) the proliferation of thymocytes in the presence of Con A under culture conditions where Con A alone is nonmitogenic, (c) the induction of antibody responses to heterologous erythrocyte antigens in athymic (nude) spleen cultures, (d) the generation of cytotoxic T lymphocytes (CTL) in thymocyte cultures, and (e) the generation of CTL in nude spleen cultures. In each of these culture systems we suggest that the assays are detecting a single class of lymphokine which acts directly on activated T cells. Nonactivated T cells must be stimulated by either antigen or mitogen before becoming responsive to lymphokine, but do not require antigen or mitogen for continued growth with lymphokine. The two molecular species, separable by isoelectric focusing are referred to as the T-cell growth factor (TCGF). A lymphokine, similar in size (30,000 daltons) to TCGF but heterogeneous in charge (pI 3.0--4.0), stimulates immune responses to erythrocyte antigens in T-cell-depleted spleen cultures but has no stimulatory activity in the other lymphocyte assay systems described. The data have been interpreted as showing the two molecular forms of murine TCGF (pI 4.3 and 4.9) are responsible for many of the lymphokine activities described elsewhere as thymocyte mitogenic factor, nonspecific T-cell-replacing factor and killer helper factor or costimulator. The other lymphokine, separable from TCGF by charge, appears to have true T-cell-replacing activity.

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“…It is noteworthy that other T-cell stimulating factors such as costimulator (Shaw et al 1978, Farrar et al 1978, T-cell growth factor (TCGF) (Watson et al 1979b) and T-cell replacing factor (Hubner et..al. The results of this analysis indicated that the active moiety in 2° MLC SN had an apparent MW of 25,000-40,000 daltons.…”

Section: Characterization Of 2° Mlc Sn Activitymentioning

confidence: 99%

“…The results of this analysis indicated that the active moiety in 2° MLC SN had an apparent MW of 25,000-40,000 daltons. It is noteworthy that other T-cell stimulating factors such as costimulator (Shaw et al 1978, Farrar et al 1978, T-cell growth factor (TCGF) (Watson et al 1979b) and T-cell replacing factor (Hubner et..al. 1978, Watson et al 1979a) have apparent molecular weights in this same range.…”

Section: Characterization Of 2° Mlc Sn Activitymentioning

confidence: 99%

Quantitation and Cloning of Cytolytic T Lymphocytes and their Precursors

MacDonald

Cerottini

Ryser

et al. 1980

Immunological Reviews

204

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Partial characterization and purification of murine T cell-replacing factor, TRF—II

Cited by 37 publications

References 7 publications

Requirement for three signals in "T-independent" (lipopolysaccharide-induced) as well as in T-dependent B cell responses.

Requirement for three signals in "T-independent" (lipopolysaccharide-induced) as well as in T-dependent B cell responses.

Biochemical and biological characterization of lymphocyte regulatory molecules. I. Purification of a class of murine lymphokines.

Quantitation and Cloning of Cytolytic T Lymphocytes and their Precursors

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