Characterization of human T suppressor‐inducer, ‐precursor and ‐effector lymphocytes in the antigen‐specific plaque‐forming cell response

Heijnen, Cobi J.; Pot, Kees H.; Ballieux, R. E.

doi:10.1002/eji.1830121012

Cited by 15 publications

(15 citation statements)

References 33 publications

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“…The induction of antigen-specific suppression using human cells has proved difficult and often unrewarding despite the recent proliferation of in vitro systems for studying regulation of specific antibody responses in man, Thus, although most investigators have used high-dose antigen as the method for attempting to generate suppressor cells [1][2][3][4], interpretation of the precise cellular mechanisms involved in subsequent inhibition of antibody production remains controversial. For example, Saxon et al [l] concluded that both T cells and B cells after in vitro incubation with high-dose tetanus toxoid were capable of transferring suppression, whereas Lane et al [2] [I 44921 implicated direct B cell tolerance as the mechanism of inhibition by high-dose keyhole limpet hemocyanin (KLH).…”

Section: Introductionmentioning

confidence: 99%

Antigen‐specific suppression of anti‐influenza antibody production in man. Possible role of a membrane‐antigen complex

McCaughan

Brown²,

Basten³

1985

Eur J Immunol

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E rosette-forming (E+) cells from human secondary lymphoid tissue were incubated with high dose influenza A virus (Mem-Bel) in an attempt to generate suppressor T cells. Suppression was assayed by transferring the antigen-pulsed E+ cells into effector cultures consisting of E+ and E- cells stimulated with immunogenic amounts of either the inducing virus Mem-Bel) or the non-cross-reacting influenza B virus (B/HK). The transfer resulted in marked inhibition of IgG, IgA and IgM antibody production to Mem-Bel but not to the control antigen, B/HK virus. The suppressive effect was specific at the level of induction as well as expression since E+ cells exposed to high dose Mem-Bel could provide help to an effector culture containing E- cells and optimal dose of B/HK virus. However, metabolically active cells did not appear to be required for suppression. Thus, it could be elicited (a) after only 15 min incubation of E+ cells with high-dose virus and (b) by E+ cells exposed to irradiation, incubated in the presence of metabolic inhibitors, or disrupted by repeated freeze thawing. In contrast, treatment of E+ cells with pronase reversed the suppressive effect. Interestingly, virus heated to 70 degree C failed to induced suppression, while retailing the ability to elicit a normal helper response. Suppression induced by exposure to standard amounts of high-dose antigen was mediated by T cells of both helper/inducer (Leu-3a+) and suppressor/cytotoxic subsets (Leu-2a+), but not by B cells. Two groups of observations pointed to the B cell as the target of suppression. First, suppression could still be transferred to effector cultures in which helper T cells had been replaced by T cell-replacing factor or suppressor T cells removed by irradiation. Second, significant inhibition of antibody production was obtained when the transfer of antigen-pulsed E+ cells was delayed for up to 120 h after initiation of the effector culture. Taken together the results suggest that suppression in this system is due to the formation of an antigen bridge between specific receptor sites on the T cell membrane and the target. Although not dependent on triggering of metabolically active suppressor T cells the phenomenon highlights the need for care in interpreting the mechanism of suppression by high-dose antigen and could, in addition, represent a biologically important control mechanism capable of rapid inhibition of effector T cells and B cells in sites of high antigen concentration.

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Section: Introductionmentioning

confidence: 99%

Antigen‐specific suppression of anti‐influenza antibody production in man. Possible role of a membrane‐antigen complex

McCaughan

Brown²,

Basten³

1985

Eur J Immunol

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“…Subsequent studies revealed that adequate helper activity could also be generated in the small subset of peripheral T lymphocytes, lacking receptors for IgM and IgG (Tfiy' cells), by stimulation with antigen in cell cultures (Table I) (Heijnen et al 1980), The T(iy'subset almost completely overlaps with the subset of peripheral blood T lymphocytes expressing affinity Tuy' cells isolated by depleting the total T cell fraction of Ifi and Ty* cells, or T//* cells isolated by rosetting with Eox-IgM complexes and subsequent density centrifugation, are cultured for 6 days in the presence of B cells, 5 % monocytes and 3//g OA/ml, When indicated ( t) the Tyuy" cells or the T/i* cells were irradiated with 1000 Rad, Cell numbersX IO' (n=3). for autologous erythrocytes (Tar*) (Heijnen et al 1982a); these T cells are considered to be postthymic precursor T lymphocytes (Palacios et al 1981). Whether the T/zy'ar* population contains mature T helper cells, lacking Fc//R, or contains T helper precursor lymphocytes is as yet unknown.…”

Section: Helper/inducer T Cells: Functional and Phenotypical Heterogementioning

confidence: 99%

“…T suppressor inducer activity. The target for the T suppressor inducer cells could be located in the Tfiy'aT* subset (Heijnen et al 1982a). The phenotypes and mode of action of the T lymphocytes in this suppressor cell circuit will be discussed in more detail in the next section.…”

Section: Pfcmentioning

confidence: 99%

“…In favour of this assumption it was found (Heijnen et al 1982b) that both T helper function and T suppressor inducer activity were insensitive to y-radiation or treatment with deoxyguanosine. Furthermore, both functional activities could be located in a subset of T^* cells, characterized by the T4 and Leu3 antigens (Heijnen et al 1982a). Corte et al (1982) reported that only a numerically minor subset of the T4'' cell population (±30%) reacts with the MoAb 5/9.…”

Section: Pfcmentioning

confidence: 99%

“…However, it seems that in present days the pendulum is swinging back. Fc-receptors as markers, in particular in conjunction with MoAb, have definite scientific value (Moretta et al 1981, Heijnen et al 1982a, Hoover & Lynch 1983. Furthermore, recent findings from several laboratories established that alloreactive cytotoxic T-cells may carry either the T8/Leu2 phenotype (originally thought to be characteristic of T lymphocytes of the suppressor/cytotoxic type) or the T4/Leu3 phenotype (originally considered to be characteristic of helper/inducer T-lymphocytes) (Moretta et al 1981, Spits et al 1982, Meuer et al 1982.…”

Section: Introductionmentioning

confidence: 99%

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Immunoregulatory T Cell Subpopulations in Man: Dissection by Monoclonal Antibodies and Fc‐Receptors

Ballieux¹,

Heijnen

1983

Immunological Reviews

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Until now, most of the studies on regulatory T cells have been based on culture systems in which human peripheral blood cells are stimulated by polyclonal stimulators like Pokeweed Mitogen (PWM). Our present contribution, however, deals with T cell-mediated regulation of the antigen-induced B cell activation, which exclusively leads to an antigen-specific IgM production (Heijnen et al. 1979a). Some authors' reports on regulatory activities of T cells, as tested in systems using polyclonal stimulators, differ from ours. This may be due to: a) as a result of polyclonal stimulus, various types of regulatory T cells are activated at the same time b) in contrast to a primary antigen, a polyclonal stimulator induces a rapid proliferation of the various regulatory T cells c) a polyclonal stimulator induces the differentiation of B cells in various maturational stages, that might each require additional or different regulatory signals. For example, Thomas et al. (1981) have shown that freshly isolated T4+ cells can induce suppressor activity in unprimed T8+ cells in the presence of PWM, whereas T4+ cells, precultured for 24 h in the presence of PWM, can exert a suppressor activity themselves without an apparent need for T8+ cells. In the antigen-specific system, however, we have neither been able to detect T suppressor effector activity in a population of primed T4+ cells, nor been able to demonstrate T suppressor inducer activity in unprimed T4+ cells (Heijnen et al. 1982a). Therefore the state of activation of the total T4+ population will dictate the balance of the total T helper and T suppressor activity. As a result of proliferation induced by polyclonal mitogens, small subsets of regulatory T cells, which are functionally undetectable in the primary antigen-specific assay, can expand sufficiently to have a measurable effect. Thomas et al. (1980) have shown that the T4+ suppressor inducer cell in the PWM system is radio-sensitive, which is in contrast with our data in the antigen-specific system. This may imply that we are looking at different subsets of T suppressor inducer cells in these different systems, but it might also indicate that T suppressor inducer cells need to proliferate in order to be able to measurably regulate the large pool of responding cells generated in the PWM system. Apart from such quantitative effects, polyclonal B cell activators like PWM are capable of inducing the differentiation of B cells in various maturational stages (Kuritani & Cooper 1982, Stevens 1982, Peters & Fauci 1983). Since it is highly likely that the regulation of these various B cell subsets might require different regulatory signals, the PWM model might be a very complicated model to study regulatory effects of single T cell subsets.(ABSTRACT TRUNCATED AT 400 WORDS)

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Antigen‐specific plaque‐forming cell response of human cord blood lymphocytes after in vitro stimulation by T cell‐dependent antigens

et al. 1983

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Mononuclear cells isolated from human cord blood (CBL) of full-term neonates were stimulated in vitro with a dose range of T cell-dependent antigens, i.e. ovalbumin or sheep erythrocytes, and tested for the capacity to mount an antigen-specific plaque-forming cell (PFC) response. Both of the antigens used induced in CBL a PFC response with the same kinetics of PFC formation and of the same magnitude as found in cultures of adult peripheral blood lymphocytes (PBL). However, optimal PFC responses in CBL were obtained at a hundredfold lower concentration of the antigens compared with the optimal antigen doses for the induction of a PFC response in adult PBL. This phenomenon was further investigated with respect to the antigen dose dependency of the activation of neonatal B cells and neonatal regulatory T cells. The induction of a PFC response in CBL at antigen concentrations that were suboptimal for adult PBL showed a correlation with the particular antigen dose requirements for the activation of B cells and T helper cells in neonates. Furthermore, the findings suggest that the decrease of the PFC response in CBL stimulated with supraoptimal doses of antigen was not caused by the induction of unresponsiveness at the B cell level or by interference of pregnancy-associated substances with the PFC response, but was rather the result of the activation of antigen-specific T suppressor cells. Neonatal T suppressor cells were activated at antigen concentrations that generated T helper activity in the adult. Thus, although neonatal B cells possess the intrinsic capacity to mature into antigen-specific PFC, the conditions for effective activation of neonatal T cells regulating the B cell response differ from those for the activation of adult regulatory T cells.

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Characterization of human T suppressor‐inducer, ‐precursor and ‐effector lymphocytes in the antigen‐specific plaque‐forming cell response

Cited by 15 publications

References 33 publications

Antigen‐specific suppression of anti‐influenza antibody production in man. Possible role of a membrane‐antigen complex

Antigen‐specific suppression of anti‐influenza antibody production in man. Possible role of a membrane‐antigen complex

Immunoregulatory T Cell Subpopulations in Man: Dissection by Monoclonal Antibodies and Fc‐Receptors

Antigen‐specific plaque‐forming cell response of human cord blood lymphocytes after in vitro stimulation by T cell‐dependent antigens

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