Proliferative Response of Clones of T Helper 1 and T Helper 2 Cells (original) (raw)
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Journal of Experimental Medicine, 1988
Murine Th1 and Th2 subsets differ not only in the lymphokines they produce, but also functionally. It is not clear what factors influence the preferential activation of one subset versus the other and what regulatory interactions exist between them. The purpose of this study was to examine the effect of lymphokines produced by clones of Th1 cells (IL-2 and IFN-gamma), Th2 cells (IL-4), and APC (IL-1) on the proliferative response of Th1 and Th2 cells after antigenic stimulation. Activation of both types of clones in the presence of antigen and APC resulted in the acquisition of responsiveness to the proliferative effects of both IL-2 and IL-4, although Th2 cells were more responsive to IL-4 than Th1 cells. Responsiveness of Th1 and Th2 cells to both lymphokines decreased with time after initial antigenic activation; Th1 cells lost their responsiveness to IL-4 more rapidly and to IL-2 more slowly than Th2 cells. IFN-gamma partially inhibited the IL-2 and IL-4-mediated proliferation o...
Clinical immunology and immunopathology, 1990
Recent studies have suggested the existence of two mutually exclusive subpopulations of T helper (Th) cells in the murine immune system, called Th1 which produces interleukin (IL)-2 and interferon (IFN)-gamma but not IL-4 and Th2 which secretes IL-4 and IL-5 but not IL-2. Also, functionally, Th1 cells generally activate the macrophages and mediate delayed-type hypersensitivity whereas Th2 cells provide help efficiently to B cells. In the present study, we investigated the lymphokine secretory properties of two well-characterized autoreactive (self-Ia reactive) T cell clones isolated from normal DBA/2 mice and autoimmune-susceptible MRL-lpr/lpr mice. It was observed that both the autoreactive T cell clones, following activation, produced IL-2, IL-4, and IFN-gamma. They induced hyper-Ia expression and cell proliferation in syngeneic B cells as well as activated the macrophages to exhibit tumoristatic properties. Both clones could also induce T-T network interaction in which syngeneic ...
Functionally distinct human T cell clones that produce lymphokines with IL-2-like activity
Human Immunology, 1984
Various functionally distinct human T cell clones derived from in vitro mixed leukozyte cultures are found to secrete lymphokines with detectable Interleukin-2 (IL-2)-like activity upon antigenic stimulation. These lymphokine producing clones are not only dependent on exogenous growth factors provided in the form of crude phytohemagglutinin (PHA)-induced spleen conditioned medium for growth but can themselves be driven to proliferate by their own lymphokines. The induction of lymphokine production appears to be antigen-specific and the lymphokines secreted are believed to contain nonantigen and nonspecies specific IL-2-1ike activity. We show here that IL-2-like lymphokines are produced by a subset ofT lymphocyte clones, i.e., the help-independent cytotoxic T cells clones that have the capacity to proliferate to, as well as to lyse, the original sensitizing cells. In addition, other T cell clones capable of producing active lymphocytes include those clones that have the T helper cell characteristics, i.e,, can undergo antigen-induced proliferation but are not cytotoxic; in the presence of lectin (PHA), however, some helper T cells (Th) but not others, can express lectin-dependent cell-mediated lysis. Finally, yet another subset of T lymphocytes, the help-dependent cytotoxic T cell clones that cannot proliferate to antigenic stimulation, was found to produce no detectable IL-2-like activity.
The Journal of Immunology
Culture supernatants generated by alloantigenic or lectin stimulation of a cloned helper T lymphocyte, designated L2, contain interleukin 2 (IL 2), granulocyte/macrophage colony-stimulating factor (CSF), B cell stimulating factor (BCSF), macrophage (Ia+)-recruiting factor (MIRF), (Ia+)-inducing activity, gamma-interferon, Fc receptor-enhancing activity, macrophage migration inhibitory factor (MIF), macrophage activation factor (MAF), interleukin 3 (IL 3), and a factor responsible for prolonging the synthesis and secretion of the fourth and second components of complement by guinea pig peritoneal macrophages. Erythropoietin was not detected. A spontaneously arising variant of L2, designated L2V, produces much lower quantities of macrophage-stimulating activities, IL 2, and interferon. However, when compared to L2, L2V produces much higher levels of BCSF, equivalent amounts of IL 3, and slightly smaller amounts of CSF. Unlike L2V, a cytolytic clone, designated L3, secretes lymphokines...
Cellular Immunology, 1988
CD3+ WT3 I T cells were sorted from peripheral blood ofa normal healthy donor by a FACS IV and cloned by limiting dilution in the presence of a phorbol ester (tetradecanoyl phorbol acetate, TPA), calcium ionophore (ionomycin, IO), interleukin-2 (IL-2) allogeneic cells, and phytohemagghttinin (PHA). One of the derived clones, 290-2, was investigated in detail. 290-2 mediated strong natural killer (NK) but not lymphokine-activated killer (LAK) activity. It proliferated in the presence of IL-2 but not IL-4. It carried the surface phenotype CD3+ WT3 l-CD4"'e"k+ CD8-, CD16-, and Leu 19+. Expression of CD4 was heterogeneous within the clone, since two of three subclones were also CD4"eak+ but one was CD4-. NK activity was blocked by monoclonal antibody (moAb) to CD1 la (LFAl), but not by monoclonal antibody (moAb) to either CD3 or CD4. Northern blotting revealed T-cell receptor (TCR-7) but not (Y-or full-length P-chain mRNA. 290-2 proliferated autonomously when stimulated with a combination of TPA + IO, with PHA or CD3 moAb and autologous B-cell lines (B-LCL) (and this was inhibited by an anti-IL-2 receptor moAb), but not to allogeneic B-LCL or any of the other stimulating agents alone. Unexpectedly, the TPA + IO stimulus which resulted in maximal proliferative responses did not trigger interferon-y or granulocyte/macrophage colony-stimulating factor production, although both lymphokines were secreted in the presence of B-LCL + TPA + IO. Proliferative responses were not enhanced by the presence of B-LCL. Thus, activation signals sufficient for autocrine proliferative responses were insufficient for secretion of other lymphokines. Such clones will provide valuable reagents for investigating the biology of the TCR--y+ T cell. o 1988
Profiles of lymphokine activities and helper function for IgE in human T cell clones
European Journal of Immunology, 1988
Profiles of lymphokine activities and helper function for IgE in human T cell clones" A large panel of phytohemagglutinin (PHA)-induced T cell clones (690 in total), established from four different human lymphoid tissues (peripheral blood, tonsils, lymph nodes and spleens) by a high-efficiency cloning technique, was characterized according to their pattern of lymphokine production. The majority of both CD4' and CD8' clones from all lymphoid tissues produced interleukin (IL) 2 and/or interferon (1FN)-y in response to 24-h stimulation with PHA. In contrast, higher proportions of IL 4-producing clones were found among CD4' clones from tonsils and spleens than from peripheral blood and lymph nodes, whereas only a minority of CD8' clones from all lymphoid tissues were found to produce IL4. It was not possible to divide the CD4' (helper/inducer) clones on the basis of their pattern of lymphokine activity into two clear-cut groups analogous to Thl and Th2 helper clones described in mice. Although 21 out of 503 (4%) CD4' T cell clones produced IL4, but not IFN-y or IL2, and 208 (41%) produced IL2 and/or IFN-y, but not IL4, a total number of 185 (37%) CD4' clones showed the ability to produce IL4 plus IL2 and/or IFNy. All types of CD4' T cells (as classified according to their pattern of lymphokine activity) provided help for IgG production in allogeneic B cells. In contrast, helper function for IgE was detectable only among the IL4-producing clones. However, the proportion of CD4' clones providing help for IgE synthesis was significantly lower among those producing IL4 and IFN-y or IL4, I L 2 and IFN-y than among those producing IL4 alone or IL4 and IL2. Thus, a clear-cut dichotomy between IL4-and IFN-y-producing Th cells, as found in mice, does not seem to exist in humans. However, I L 4 and IFN-y, even if not always produced by distinct T cell subsets, appear to regulate reciprocally the synthesis of IgE in humans as well. * This work was supported by grants from CNR (finalized project 87.01429.44 and grant 87.01508.04), Ministery of Education (12-02-01355 and 12-02-01504).
Cellular Immunology, 1991
In this present study, lymphokine (IL-2/1L-4) production in VSV-induced Th cell (L3T4'Lyt-2-VW-immune T cells) and memory CTL populations (L3T4-Lyt-2+ VSV-immune T cells) has been assessed in order to gain some understanding as to why the Lyt-2' subset (L3T4-independent Th cell pathway) fails to provide Th cell function for anti-VW CTL responses. Our studies demonstrated that following specific antigen (VSV, H-2 antigen) or mitogen stimulation. lymphokine activity was detected in the supernatants obtained from VSV-induced Th but not VSV memory CTL populations. The presence of blocking concentrations of PC6 1, a monoclonal antibody (mAb) to the IL-2 receptor (IL-2R), revealed augmented lymphokine activity only in the VSV-induced Th cell supematant. VSV-induced Th ceils secreted both IL-2 and IL-4 following stimulation with VSV. Two lines of evidence supported the view that both these lymphokines were important for an anti-VSV CTL response: (1) mAb to either IL-2 or IL-4 inhibited CTL maturation and (2) the combination of exogenous IL-2 and IL-4 reconstituted a class I-restricted. VSV-specific CTL response in Th cell-depleted T cell cultures. The failure to detect lymphokine production in bulk cultures of the VSV memory CTL population was consistent with limiting dilution (LD) analysis of lymphokine-producing cells in the spleen of VSV-immune mice. Thus. approximately l/l 5,000 Lyt-2-depleted, VSV-immune T ceils were positive for lymphokine production following VSV stimulation. whereas i l/l ,OOO,OOO L3T4-depleted. VSV-immune T cells were scored as lymphokine-secreting cells following stimulation with this same virus. Similarly, precursor estimates for lymphokine-producing cells against allogeneic class I antigens demonstrated that the majority of lymphokine-producing cells also resided in the L3T4+ subset. Lymphokinesecreting Lyt-2+ cells were detected at low but not high cell densities suggesting that Lyt-2+ cells may secrete another lymphokine(s) that inhibits IL-2/IL-4 production. Thus, these studies demonstrate an obligatory requirement for the L3T4-dependent Th cell pathway for optimal CTL responses derived from either CTLp or memory CTLs.