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S O Sharrow

Publications and source records attributed to S O Sharrow.

At least 55 records · Page 3Linked to original sources
PubMed1989

Effect of cyclosporin A on lymphopoiesis. I. Absence of mature T cells in thymus and periphery of bone marrow transplanted mice treated with cyclosporin A.

In this report, we investigate the effect of cyclosporin A (CsA) on lymphopoiesis, and demonstrate that CsA selectively abrogates the development of CD4+CD8- and CD4-CD8+ T cells (single positive cells) in the thymus. This developmental arrest results in the complete absence of mature T cells (assessed both by phenotypic and functional analyses) in the spleen of syngeneic bone marrow transplanted mice subsequently treated with CsA. In contrast to its remarkable effect on T cells, CsA had no detectable effect on B cells differentiation. In the thymus, the generation of CD4+CD8+ thymocytes was not affected by CsA treatment, and CD4-CD8- thymocytes of CsA-treated mice expressed surface markers characteristic of normal CD4-CD8- thymocytes, and exhibited normal functional activity when stimulated with anti-CD3 antibody. Thus, CsA appears to prevent the generation of mature, single positive T cells without affecting the development of immature T cells in the thymus. In addition to its immunosuppressive effect on immunocompetent cells, these results indicate a novel feature of CsA, which involves arrest of T cell differentiation, a finding that may be important for applications in clinical bone marrow transplantation.

Animals↗
PubMed1989

Effect of cyclosporin A on T cell immunity. II. Defective thymic education of CD4 T helper cell function in cyclosporin A-treated mice.

Cyclosporin A (CsA) is an immunosuppressive agent that is widely used in transplantation. Recent animal studies indicate that CsA can affect the development of immunity so that autoreactive T lymphocytes are generated. In this study, mice were treated with CsA prior to irradiation and transplantation of syngeneic bone marrow to determine whether CsA pretreatment would affect the ability of the bone marrow recipients to develop normal T cell function. Our results indicate that (a) thymuses of CsA-treated mice do not contain single-positive thymocytes (i.e. L3T4+Ly-2- or L3T4-Ly-2+) during i.p. treatment with 15 mg/kg/day of CsA; (b) both populations of single-positive thymocytes reappear within 2 weeks of termination of CsA and (c) irradiation and bone marrow reconstitution of these CsA-treated mice results in reconstitution of normal numbers of L3T4+ and Ly-2+ cells, but the L3T4+ T cells to not provide T helper function, as determined by interleukin 2 production and cytotoxic T lymphocytes generation. These findings indicate that CsA can affect thymic microenvironment and may be important as a model for investigating intrathymic T cell maturation. Our results may also have clinical implications for T lymphocyte development in transplant patients receiving CsA.

Animals↗
PubMed1989

Expression of a class I MHC transgene: effects of in vivo alpha/beta-interferon treatment.

Transgenic mice containing a swine class I major histocompatibility complex (MHC) gene, PD1, express swine MHC (SLA) antigen. The tissue distribution of PD1 RNA parallels that observed in the swine, indicating that the expression of PD1 is regulated and that trans-acting factors involved in this regulation have been conserved between the species. Although PD1 RNA levels were much greater in transgenic spleen than in thymus, no difference in the chromatin organization of the PD1 gene was detected. In both tissues, a single DNase I hypersensitive site mapped within the 5' flanking region. In vivo treatment of the transgenics with mouse alpha, beta-interferon increases PD1 expression in a number of tissues. In the spleen, this increase parallels that observed for the endogenous transplantation antigen, Kb, but differs markedly from the differentiation antigen, Qa-2. Increases in cell surface expression of both PD1 and Kb occurred equally in splenic T- and B-cell populations following alpha, beta-interferon treatment. In contrast, Qa-2 expression in B cells was enhanced by alpha, beta-interferon, whereas it was unaffected in T cells and thymocytes.

Animals↗
PubMed1989

Cardiac allograft survival across major histocompatibility complex barriers in the rhesus monkey following T lymphocyte-depleted autologous marrow transplantation. IV. Immune reconstitution.

Studies of postmyeloablative immune reconstitution have been reported for allogeneic bone marrow transplantation and also for non-T cell-depleted autologous/syngeneic BMT. However, there is a paucity of information regarding immune recovery following T cell-depleted autologous/syngeneic BMT. We have developed a primate transplantation tolerance model in which rhesus monkeys were conditioned with total-body irradiation and extensively T cell-depleted autologous BMT and given a major histocompatibility complex-mismatched heterotopic cardiac allograft. This model provided an opportunity to study peripheral immune recovery following T cell-depleted autologous BMT. Limiting dilution analysis was used to quantify marrow T cells following depletion (2.8% to 25.6% marrow T cells predepletion, 0.00014% to 0.036% residual marrow T cells postdepletion). We found that (1) hematopoietic engraftment was prompt despite extensive marrow T cell depletion, (2) reconstitution of CD4+ helper T cells and CD8+ cytotoxic T cells were substantially delayed (6-12 months) compared with the recovery of CD8+ suppressor T cells, CD16+ NK cells, and CD20+ B cells, (3) distinction between CD8+ cytotoxic T cells and CD8+ suppressor T cells by the CD28 marker was critical in revealing the markedly discrepant recoveries of those subsets, and (4) immune reconstitution resembled that observed in recipients of T cell-depleted allogeneic and non-T cell-depleted autologous/syngeneic BMT, suggesting that the pattern of immune recovery following BMT is not substantially influenced by either allogeneic effects or the number of transferred T cells over a range of values.

Animals↗
PubMed1988

Engagement of the CD4 molecule influences cell surface expression of the T-cell receptor on thymocytes.

The intrathymic differentiation process by which precursor cells derived from the bone marrow develop into immuno-competent T lymphocytes is poorly understood. Most thymocytes express both CD4 and CD8 accessory molecules, yet little is known about either the function of these molecules or the responsiveness of the CD4+8+ double positive thymocytes that bear them. Here, we address the possibility that CD4 engagement influences T-cell receptor (TCR) expression on developing thymocytes. We engaged CD4 molecules on murine thymocytes by in vivo injection of an anti-CD4 monoclonal antibody, which reduced the surface expression of CD4 on CD4+ thymocytes. More importantly, CD4 engagement also affected TCR expression on CD4+ thymocytes, but the effect on CD4+8+ double positive and CD4+8- single positive thymocytes was very different. CD4+8+ thymocytes responded to CD4 engagement by dramatically increasing surface expression of TCR, whereas CD4+8- thymocytes decreased surface expression of TCR. These results demonstrate that the effect of CD4 engagement on TCR expression is dependent upon the developmental state of the responding thymocyte, and, most interestingly, results in increased TCR expression by double positive thymocytes.

Animals↗
PubMed1988

Differentiation of Ia-reactive CD8+ murine T cells does not require Ia engagement. Implications for the role of CD4 and CD8 accessory molecules in T cell differentiation.

The present study was undertaken to assess the Ia differentiation requirements of CD8+ class II-allospecific CTL, whose CD8+ phenotype is apparently "discordant" with their MHC class II reactivity. To do so, we compared the effect of in vivo anti-Ia blockade on the differentiation of Ia-reactive CD8+ CTL with its effect on the differentiation of CD4+ T cells. We found that anti-Ia blockade did not detectably interfere with the differentiation of CD8+ Ia-reactive CTL, even though it arrested the differentiation of CD4+ T cells. Thus, the differentiation of CD4+ T cells is strictly dependent upon Ia engagement, whereas the differentiation of CD8+ T cells, even those with reactivity against MHC class II alloantigens, does not require Ia engagement. These results support the concept that Ia-reactive CD8+ T cells are conventional CD8+ CTL, probably selected by self-class I MHC molecules during differentiation, whose receptors fortuitously crossreact on MHC class II alloantigens. Taken together, the present data indicate an intimate relationship between CD4/CD8 expression with MHC class specificity during T cell differentiation and selection. We suggest that an active triggering role for CD4 and CD8 accessory molecules in T cell differentiation is best able to explain these observations.

Animals↗
PubMed1988

Role of L3T4+ and Lyt-2+ donor cells in graft-versus-host immune deficiency induced across a class I, class II, or whole H-2 difference.

The i.v. injection of parental T cells into F1 hybrid mice can result in a graft-vs-host (GVH)-induced immune deficiency that is Ag nonspecific and of long duration. The effect of the GVH reaction (GVHR) on the host's immune system depends on the class of F1 MHC Ag recognized by the donor cells. To determine the role of different subsets of donor-derived T cells in the induction of GVHR, donor spleen cells were negatively selected by anti-T cell mAb and C, and the cells were injected into F1 mice that differed from the donor by both class I and II MHC Ag or by class I or class II MHC only. The induction of GVHR across class I + II differences was found to require both L3T4+ and Lyt-2+ parental cells. Induction of GVHR across a class II difference required only L3T4+ parental T cells in the combination tested [B6-into-(B6 x bm12)F1]. In contrast, B6 Lyt-2+ cells were sufficient to induce GVHR across a class I difference in (B6 x bm1)F1 recipients. In addition, a direct correlation was observed between the cell types required for GVH induction and the parental T cell phenotypes detected in the spleens of the GVH mice. The number of parental cells detected in the unirradiated F1 hosts was dependent upon the H-2 differences involved in the GVHR. Induction of a class I + class II GVHR resulted in abrogation of both TNP-self and allogeneic CTL responses. In contrast, induction of a class II GVHR resulted in only a selective loss of TNP-self but not of allogeneic CTL function. Unexpectedly, the induction of a class I GVHR also resulted in the selective loss of the TNP-self CTL response. Thus, these class I and class II examples of GVH both result in the selective abrogation of L3T4+ Th cell function. The data are discussed in terms of respective roles of killer cells and/or suppressor cells in the induction of host immune deficiency by a GVHR, and of the selective deficiency in host Th cell function induced by different classes of GVHR.

Animals↗
PubMed1988

Human memory T lymphocytes express increased levels of three cell adhesion molecules (LFA-3, CD2, and LFA-1) and three other molecules (UCHL1, CDw29, and Pgp-1) and have enhanced IFN-gamma production.

Studies of cell-surface molecules involved in human T cell interaction reveal that differential expression of each of three adhesion molecules (LFA-3, CD2, and LFA-1) subdivides human peripheral blood T cells into major subpopulations. Systematic analysis of the relationship between expression of these and other markers of T cell subsets demonstrates a single major subset of human peripheral blood T lymphocytes distinguished by enhanced expression of LFA-3, CD2, LFA-1, and three other markers (CDw29 [4B4], UCHL1, and Pgp-1). Large differences in relative expression are observed for UCHL1 (29-fold) and LFA-3 (greater than 8-fold), and smaller differences (2- to 4-fold) are seen for CDw29, CD2, LFA-1, and Pgp-1. Bimodal distribution of LFA-3 is found on both CD4+ cells and on CD8+ cells as well as on B lymphocytes (CD19+). Neonatal T cells (CD3+) are comprised almost exclusively of the subset expressing low LFA-3, CD2, LFA-1, CDw29, and UCHL1. Activation of cord peripheral blood mononuclear leukocytes with PHA leads to uniform enhanced expression of each of these molecules on CD3+ cells. Functional analyses of these T cell subsets were performed after sorting of adult T cells based on differential LFA-3 expression. Only the LFA-3+ subset proliferated in response to the Ag tetanus toxoid, even though the LFA-3- subset proliferated more strongly to PHA. Furthermore, the LFA-3+ subset made greater than fivefold more IFN-gamma than the LFA-3- subset in response to PHA, despite the fact that both subsets made equivalent amounts of IL-2. This phenotypic and functional analysis of resting and activated newborn and adult T cells indicates that human memory T cells express enhanced levels of LFA-3, CD2, LFA-1, UCHL1, CDw29, and Pgp-1; we speculate that the increase in expression of T cell adhesion molecules LFA-3, CD2, and LFA-1 on memory cells is functionally important in their enhanced responsiveness.

Adult↗
PubMed1988

Nonequivalent effects of PKC activation by PMA on murine CD4 and CD8 cell-surface expression.

The membrane glycoproteins CD4 (L3T4) and CD8 (Lyt2) are expressed on distinct populations of mature murine T lymphocytes, and are thought to be receptors for monomorphic determinants expressed on MHC class II and class I molecules, respectively. Although they differ in their ligand specificity, it has been presumed that CD4 and CD8 perform equivalent functions in the T cells that bear them. Since activation of protein kinase C (PKC) is known to cause rapid down-regulation of various receptors, including the T cell receptor complex (TcR complex), we treated cells with phorbol 12-myristate 13-acetate (PMA), a PKC activator, to determine whether cell-surface expression of CD4 and CD8 would be similarly affected by this intracellular mediator. Brief or relatively prolonged treatment with PMA induced mature murine T cells to reduce their surface expression of the TcR complex and of CD4, but not of CD8. Similarly, PMA rapidly induced transfected L cells to down-regulate surface CD4 expression, but had no effect on surface CD8 expression. Most significantly, PMA treatment induced CD4+CD8+ immature thymocytes to rapidly reduce their surface CD4 expression, but, again, it had no immediate effect on the surface expression of CD8. These results indicate that CD4 and TcR complex cell-surface expression are both sensitive to PKC activation by brief treatment with PMA, whereas CD8 expression is not, and suggest that CD4 and CD8 surface expression levels are regulated by distinct intracellular mechanisms.

Animals↗
PubMed1988

Therapy of patients with human T-cell lymphotrophic virus I-induced adult T-cell leukemia with anti-Tac, a monoclonal antibody to the receptor for interleukin-2.

Human T-cell lymphotropic virus I (HTLV-I)-induced adult T-cell leukemia (ATL) cells constitutively express interleukin-2 (IL-2) receptors identified by the anti-Tac monoclonal antibody (MoAb), whereas normal resting cells do not. This observation provided the scientific basis for a trial of intravenous anti-Tac in the treatment of nine patients with ATL. The patients did not suffer untoward reactions and did not have a reduction in the normal formed elements of the blood, and only one of the nine produced antibodies to the anti-Tac MoAb. Three patients had transient mixed, partial, or complete remissions lasting from 1 to more than 8 months after anti-Tac therapy, as assessed by routine hematologic tests, immunofluorescence analysis of circulating cells, and molecular genetic analysis of HTLV-I provirus integration and of the T-cell receptor gene rearrangement. The precise mechanism of the antitumor effects is unclear; however, the use of a MoAb that prevents the interaction of IL-2 with its receptor on ATL cells provides a rational approach for the treatment of this malignancy.

Adult↗
PubMed1988

Effects of heparin on in vitro immune parameters.

The effects of heparin on several in vitro immune functions [blastogenesis, interleukin-2(IL-2) production] were investigated. The addition of heparin to human peripheral mononuclear cells stimulated with phytohemagglutinin or pokeweed mitogen significantly increased the blastogenic response of these cells. Peak IL-2 concentrations in the supernatant of heparin-containing cultures were two- to fourfold higher than in heparin-free cultures. Flow cytometry experiments revealed that Leu-M3-positive cells were the only subset to be significantly affected by heparin, which induced an increase both in number and in fluorescence intensity of Leu-M3-positive cells. In contrast, the expression of DR molecules on monocytes was slightly decreased. It is speculated that the observed antimetastatic effects of heparin may be exerted through local immunomodulation in macrophage-rich tissues.

Heparin↗
PubMed1987

Enhanced antigen-presenting capacity of cultured Langerhans' cells is associated with markedly increased expression of Ia antigen.

Recent studies indicate that when epidermal Langerhans' cells (LC) are cultured for 2 to 3 days they, in comparison to freshly prepared LC, exhibit markedly enhanced ability to stimulate T cell proliferative responses in oxidative mitogenesis and in the mixed epidermal-leukocyte reaction. In this study, we determined whether cultured LC enhance antigen-specific T cell responses, and whether such enhanced stimulatory capacity correlates with the level of Ia antigen expressed on LC. We used C3H/He (Iak) epidermal cells as stimulators and, as responder cells, both the trinitrophenyl-specific clones D8 and SE4, which were assayed for [3H]dThd incorporation, and the pigeon cytochrome c specific hybridoma 2C2, which was assayed for interleukin 2 production. Cultured LC induced 10 to 100 times greater proliferation or interleukin 2 production by responder cells than did freshly prepared LC. The intensity of I-Ak and I-Ek, expressed on cultured LC as assessed by immunofluorescence and flow cytometry, was found to be 10 to 36 times greater on a per cell basis than that on freshly prepared LC. Depletion of LC from fresh epidermal cell suspensions by anti-Iak and complement or treatment with 50 mJ/cm2 medium range ultraviolet light or cycloheximide before culture abrogated both the increase in Ia expression and antigen-specific clonal proliferation. The results suggest that when LC are removed from their usual epidermal milieu, they express increased amounts of Ia and become more potent stimulators of T cell responses.

Animals↗
PubMed1987

Role of cytotoxic T lymphocytes in the prevention of lupus-like disease occurring in a murine model of graft-vs-host disease.

The inoculation of B6D2F1 mice with T lymphocytes from the C57BL/6 parental strain induces an "immunosuppressive" graft-vs-host reaction (B6 GVH), whereas inoculation of T cells from the other, DBA/2 parental strain induces an "immunostimulatory" GVH reaction and a lupus-like disease (DBA GVH). The present study compares cytotoxic T lymphocyte (CTL) function in the spleens of these GVH mice as well as differences in the donor inoculum that could account for these different types of GVH. We observed that the B6 GVH induces an immunodeficiency that encompasses CTL precursors (and possibly T helper cells) and results in suppressor cells that abrogate responses to both trinitrophenyl (TNP)-modified self and third party alloantigens. In contrast, the DBA GVH induces only a T helper cell immunodeficiency and results in suppressor cells selective for class II restricted L3T4+ T helper cells. Chimeric T cells were detected in both types of GVH. In the B6 GVH both L3T4+ and Lyt-2+ donor cells were observed, although Lyt-2+ cells predominated. In the DBA GVH, donor T cells were almost exclusively of the L3T4+ phenotype. The lack of appreciable donor Lyt-2+ cells in the DBA GVH can be explained by a defect in the DBA donor inoculum manifested by a naturally occurring two-fold reduction in Lyt-2+ cell numbers as well as a nine-fold reduction in CTL precursors with anti-F1 specificity. T cells in the DBA inoculum, therefore, are predominantly L3T4+. A similar defect induced in B6 donor cells by anti-Lyt2 antibody and complement not only converted the suppressive GVH to a stimulatory GVH, as measured by anti-DNA antibodies, but also resulted in a T cell immune deficiency characteristic of the DBA GVH, i.e., a selective loss of the TNP-self CTL response. Thus the presence or absence of adequate numbers of functioning Lyt-2+ cells in the donor inoculum is correlated with the development of either a suppressive or stimulatory GVH, respectively. That donor Lyt-2+ cells mediate a suppressive GVH through cytolytic mechanisms is evidenced by greater than 70% reduction in B6 GVH spleen cell numbers and readily demonstrable anti-F1 CTL activity by these spleen cells despite an inability to generate anti-allogeneic or anti-TNP self CTL activity even in the presence of added T helper factors.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

Phenotype, specificity, and function of T cell subsets and T cell interactions involved in skin allograft rejection.

In the present study we used an adoptive transfer model with athymic nude mice to characterize the T cells involved in initiating and mediating skin allograft rejection. It was found that skin allograft rejection in nude mice required the transfer of immunocompetent T cells and that such reconstitution did not itself stimulate the appearance of T cells derived from the nude host. Reconstitution with isolated populations of Lyt-2+/L3T4- T cells resulted in the rapid rejection of MHC class I-disparate skin allografts, whereas reconstitution with isolated populations of L3T4+/Lyt-2- T cells resulted in the rapid rejection of MHC class II-disparate and minor H-disparate skin allografts. By correlating these rejection responses with the functional capabilities of antigen-specific T cells contained within the reconstituting Lyt-2+ and L3T4+ T cell populations, it was noted that skin allografts were only rejected by mice that, as shown by in vitro assessment, contained both lymphokine-secreting Th cells and lymphokine-responsive Tk cells specific for the alloantigens of the graft. The ability of two such functionally distinct T cell subsets to interact in vivo to reject skin allografts was directly demonstrated in H-Y-specific rejection responses by taking advantage of the fact that H-Y-specific Th cells are L3T4+ while H-Y specific Tk cells are Lyt-2+. Finally, the importance of in vivo interactions between functionally distinct Th/T-inducer cells and T killer (Tk)/T-effector cells in skin allograft rejection was demonstrated by the observation that normal B6 mice retain Qala and Kbm6 skin allografts because of a selective deficiency in antigen-specific Th cells, even though they contain T-effector cells that, when activated, are able to reject such allografts. Thus, the ability to reject skin allografts is neither unique to a specialized subset of T cells with a given Lyt phenotype, nor unique to a specialized subset of helper-independent effector T cells with so-called dual function capability. Rather, skin allograft rejection can be mediated by in vivo collaborations between T-inducer cells and T-effector cells, and the two interacting T cell subsets can express different Lyt phenotypes as well as different antigen specificities.

Animals↗
PubMed1987

In vivo administration of purified human interleukin-2 to patients with cancer: development of interleukin-2 receptor positive cells and circulating soluble interleukin-2 receptors following interleukin-2 administration.

Recent studies have demonstrated efficacy of immunotherapies including interleukin-2 (IL-2) in the treatment of malignancies in rodents and humans. High levels of IL-2 receptor-positive cells were found in the peripheral blood of patients receiving recombinant IL-2 in these Phase I clinical trials. This was demonstrated both in patients receiving i.v. IL-2 who had detectable circulating levels of IL-2 as well as in patients receiving i.p. IL-2 who did not. Up to 100% of the anti-Tac binding could be inhibited by preincubation with IL-2 indicating that this was indeed an IL-2 receptor that was identified. Two-color experiments demonstrated that few Leu 2-positive cells (less than 5-10%) but over 30% of the Leu 3-positive cells bore Tac antigen. Most of the M3-positive monocytes were Tac positive (83.7%) and negative for other T-cell (Leu-4) and nonspecific murine markers (Lyt-2 and Thy 1.2). Although normal individuals had a mean of only 186 units/ml (range, 83-335 units/ml) of soluble IL-2 receptor, patients receiving IL-2 had as much as 20,000 units/ml of soluble IL-2 receptor line in their serum. The physiological role of the IL-2 receptor identified on the cell surface of Leu 3 and M3-positive cells as well as in the serum is unclear. Soluble IL-2 receptors appeared in the circulation early following IL-2 administration, approximately 1 week prior to the detection of circulating IL-2 receptor-bearing cells. Further studies will be needed to assess the role of IL-2 in monocyte function, the precise function of IL-2 receptor-bearing Leu 3-positive cells, and the relationship of these findings to the toxicity and success of this immunotherapy in humans.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1987

Subpopulations of mouse Lyt-2+ T cells defined by the expression of an Ly-6-linked antigen, B4B2.

The production and characterization of a rat mu,kappa monoclonal anti-mouse T cell subset antibody, B4B2, is reported in this paper. B4B2 typing of lymphoid tissues of commonly used inbred mouse strains revealed two types of reactivity patterns. They can be characterized as C57BL/6-like (B6-like) or C3H/He-like (C3H-like). Among B6-like strains, B4B2 recognizes 5 to 10% of spleen cells, 30 to 50% of bone marrow cells, and less than 2 to 3% of thymocytes. In C3H-like strains, B4B2 reacts with less than 1% of spleen cells, 2 to 8% of bone marrow cells, and less than 1% of thymocytes. B4B2 recognizes a T cell subset differentiation antigen expressed by B6-like strains but not by C3H-like strains. Typing of BXH recombinant inbred strains showed linked expression of B4B2 and the Ly-6 antigen. The expression of B4B2 antigen appears to be under codominant control as the median fluorescence distribution of B4B2+ cells in C57BL/6 was approximately twice that of (C57BL/6xC3H)F1. B4B2 was shown to react with approximately 40 to 50% of Lyt-2+ T cells and less than 1% of L3T4+ T cells. No staining of resting or activated B cells by B4B2 was detected. The ratio of B4B2+:Lyt-2+ cells was similar for resting T cells and activated T cells obtained from mitogen-stimulated cultures or mixed lymphocyte cultures. In neonatal spleen, substantially more B4B2+ than Lyt-2+ cells were found. With increasing age, however, a rapid decline in B4B2+ cells and a corresponding increase of Lyt-2+ cells was observed. By approximately 1 mo of age, the relative proportion of these subsets had reversed so that Lyt-2+ cells became more numerous than B4B2+ cells.

Age Factors↗
PubMed1987

Graft-vs-host reaction limited to a class II MHC difference results in a selective deficiency in L3T4+ but not in Lyt-2+ T helper cell function.

Hybrid mice of the (B6 X bm12)F1 combination were inoculated i.v. with parental B6 spleen cells to induce a class II graft-vs-host disease (GVH). Such mice failed to generate in vitro cytotoxic T lymphocyte (CTL) responses that were dependent upon L3T4+ T helper cell (Th) function (e.g., anti-B6-TNP) but were capable of generating in vitro CTL responses that could be mediated by Lyt-2+ Th cells (anti-allo class I). When Th function was assayed directly by interleukin 2 (IL 2) secretion, class II GVH animals were found to be deficient in L3T4+ but not Lyt-2+ IL 2-secreting Th cells. This selective deficiency in L3T4+ Th function correlates with a selective decrease in class II GVH mice of host-derived derived L3T4+ T cells. In addition, it was found that the spleens of class II GVH mice contained cells capable of selectively suppressing L3T4+ Th function. In contrast, mice in which a class I + II GVH occurred were depleted of both L3T4+ and Lyt-2+ Th function as assessed by IL 2 production. The findings that class II GVH selectively depletes L3T4+ T cells and T cell functions are discussed with respect to the immune function of distinct T cell subsets in normal and diseased states.

Animals↗