Strong lymphoproliferative suppressive function of PLT clones specific for SB-like antigens

Pawelec, Graham; Wernet, Peter; Rosenlund, R.; Blaurock, M; Schneider, E. M.

doi:10.1016/0198-8859(84)90042-9

Cited by 22 publications

(16 citation statements)

References 17 publications

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“…However, these data may be consistent with results supporting the existence of a second "DP-like" locus (Lee & Trowsdale 1983, Pawelec et al 1982a, Pawelec et al 1984a). It will be of interest to examine the functional attributes of clones specific for such different LADS, since a striking feature of PLT clones specific for "DP-like" determinants as opposed to DP or DWDw determinants, has been the strong suppressive activity only of the former for proliferative responses in primary and secondary MLC (Pawelec et al 1984a). Preliminary evidence indeed suggests that the PLT clones responding to putative DP-like determinants described here can also suppress primary MLC.…”

Section: Discussionsupporting

confidence: 89%

The new HLA‐DRw6‐ and 8‐ associated HLA‐Dw HAG specificity defined by homozygous typing cell 9W 1802

et al. 1984

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Intrafamilial primary mixed lymphocyte culture (MLC) typing established that an HLA-A, B, C homozygous, DP heterozygous donor HAG was homozygous for HLA-Dw and behaved as a homozygous typing cell (HTC). Both haplotypes of the HTC were HLA-DR identical, but could not be assigned a clear DR specificity, giving reactions with sera containing antibodies against DRw6, DRw8 and TA10. MLC checkerboard studies failed to assign the HTC HAG specificity to any established or provisional cluster, suggesting that it defined a new Dw specificity. Primed lymphocyte typing (PLT) clones derived from intra-familial priming against either HAG haplotype displayed heterogeneous reactivity patterns. One clone was restimulated only by family members and unrelated donors positive for Dw HAG. Other clones were restimulated by determinants associated with either Dw8 or Dw6. Blocking of stimulation with monoclonal antibodies against different class II molecules suggested that while stimulatory determinants associated with Dw HAG and Dw8 were classifiable as HLA-D related, those associated with Dw6 were of a DP-like nature.

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Section: Discussionsupporting

confidence: 89%

The new HLA‐DRw6‐ and 8‐ associated HLA‐Dw HAG specificity defined by homozygous typing cell 9W 1802

et al. 1984

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“…Some of the difficulties experienced in generating SB-specific PLT reagents, and the high proportion of suppressive clones derived from HLA-A, B, C, DWDw-matched. SBmismatched priming combinations may still reflect a preferential activity of SB or SB-like antigens in triggering suppression [17]. These antigens, rather than D C or DR antigens, could thus play a critical part in negative feedback regulation of human cellular immune responses.…”

Section: Pbmc Stimulated By Activated T Cell Clones Mediate Strong Sumentioning

confidence: 99%

Cloned human T lymphocytes with lymphostimulatory capacity preferentially activate suppressor cells

1984

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A proportion of cloned T cells derived from allogeneic mixed leukocyte cultures (MLC) was found to stimulate rapid primary, but not secondary, lymphoproliferative responses of autologous as well as allogeneic peripheral blood mononuclear cells (PBMC). Of eight major histocompatibility complex (MHC) class II-specific monoclonal antibodies (mAb), the reagent TU39 (which preferentially inhibits allostimulation by SB- rather than DR- or DC-associated determinants) most strongly inhibited stimulation by these clones. MAb specific for DC or DR molecules inhibited weakly or not at all. Stimulatory, but not nonstimulatory, clones were found to be strongly suppressive when titrated directly into MLC. Suppression was no MHC restricted, was radioresistant (20 Gy) and was not abrogated by the addition of partially purified interleukin 2 to the test cultures. Transfer of PBMC cocultured with stimulatory, but not with nonstimulatory, clones into a second MLC resulted in its strong suppression, suggesting that a suppressor effector population had been "induced" by the clones. These results are consistent with the hypothesis that SB-like, rather than DR or DC, determinants present on the surface of certain activated T cells are intimately involved in the regulation of cellular immune responses by rapidly inducing suppressor effector cells in normal lymphocyte populations.

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“…HLA-SB is henceforth to be known as HLA-DP and HLA-DC as HLA-DQ. also been documented in this [4] and other [7] laboratories. Therefore, a screening for the regulatory activity on lymphoproliferative (LP) responses, either enhancing or suppressive, of a number of PLT clones specific for determinants encoded by different class I1 loci has been undertaken, using clones from three sources: (a) primary mixed lymphocyte culture (MLC) between HLA-D-mismatched donors -the majority of PLT clones recognized lymphocyte-activating determinants (LAD) mapped to the D region [3]; (b) tertiary MLC between HLA-D-matched, SB-mismatched donors -the majority of PLT clones recognized LAD indistinguishable from SB products [8], and (c) primary MLC between HLA-D-matched SBmismatched donors -some PLT clones recognized MB-associated LAD, some recognized SB-associated LAD, but the majority recognized LAD not associated with DR/Dw, MB, MT or SB determinants.…”

Section: Introductionmentioning

confidence: 75%

“…The existence of at least three, and very probably more, distinct subsets of human major histocompatibility complex (MHC) class I1 molecules encoded by discrete genetic loci has been clearly established, namely HLA-D, DC or MB and SB; the products may function as alloantigens and as restriction elementsin antigen presentation for proliferative responses of T lymphocytes. However, it remains to be determined whether T cells reactive to different class I1 molecules are endowed with different functional activities, since proliferative capacity cannot be equated with a particular functional status, even when the clones carry a T4+, T8-, Leu 8-surface phenotype [4]. Several reports do suggest that at least a majority of alloproliferative, primed lymphocyte typing (PLT), clones can have helper function for antibody production [5, 61, but the existence of suppressive PLT clones has [I 45971 * Supported by DFG SFB 120 (Al, A2, Cl).…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, a screening for the regulatory activity on lymphoproliferative (LP) responses, either enhancing or suppressive, of a number of PLT clones specific for determinants encoded by different class I1 loci has been undertaken, using clones from three sources: (a) primary mixed lymphocyte culture (MLC) between HLA-D-mismatched donors -the majority of PLT clones recognized lymphocyte-activating determinants (LAD) mapped to the D region [3]; (b) tertiary MLC between HLA-D-matched, SB-mismatched donors -the majority of PLT clones recognized LAD indistinguishable from SB products [8], and (c) primary MLC between HLA-D-matched SBmismatched donors -some PLT clones recognized MB-associated LAD, some recognized SB-associated LAD, but the majority recognized LAD not associated with DR/Dw, MB, MT or SB determinants. The latter were designated "SB-like" [4] on the basis of patterns of stimulation inhibition with a panel of monoclonal antibodies (mAb) specific for different subsets of class I1 molecules. Since all PLT clones specific for SB-like products, but almost none specific for other class I1 determinants, strongly suppressed LP responses, this suggests a better correlation between the functional status of responding T cell clones and their type of stimulating antigen, than between a particular surface phenotype and a certain function.…”

Section: Introductionmentioning

confidence: 99%

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Function of alloproliferative T lymphocyte clones correlates better with their class II recognitive specificity than with their cell surface phenotype

1985

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Alloproliferative primed lymphocyte typing (PLT) clones recognizing determinants associated with HLA-DR/Dw, SB, MB, or novel "SB-like" gene products were screened for their ability to suppress lymphoproliferative responses in primary and secondary mixed lymphocyte cultures (MLC), and for their surface marker phenotypes. Two nonsuppressive HLA-D specific PLT clones were OKT4-, OKT8+ whereas all others possessed an OKT4+, OKT8-, Leu-8- phenotype. All clones secreted interleukin 2 (IL2) after specific stimulation. The eight PLT clones specific for "SB-like" antigens strongly suppressed MLC, whereas only one of 35 DR/Dw-specific, and none of 20 SB-specific PLT clones did so. Suppressive activity of such PLT clones was not restricted by major histocompatibility complex products, was radioresistant (20 Gy), and was not caused by absorption of IL2 or by cytotoxicity of the cloned cells. Suppressive clones exerted their effects directly on proliferating T cells, as assessed by their ability to prevent growth of cloned PLT cells stimulated by B cell lines, and their ability to block primary MLC even when added 96 h after the start of the 144-h culture. Culture supernatants from suppressive, but not from nonsuppressive, PLT clones also strongly and nonspecifically inhibited lymphoproliferative responses. The suppressive factor(s) was not dialyzable, not sensitive to pH 2 or heat treatment and not cytotoxic. Thus, all T cell clones proliferating against novel "SB-like" but not SB antigens, as well as rare clones specific for D region determinants, possess powerful nonspecific suppressive activities dissociated from their "helper-related" OKT4+, OKT8-, Leu 8-, IL2-secreting phenotypes.

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Strong lymphoproliferative suppressive function of PLT clones specific for SB-like antigens

Cited by 22 publications

References 17 publications

The new HLA‐DRw6‐ and 8‐ associated HLA‐Dw HAG specificity defined by homozygous typing cell 9W 1802

The new HLA‐DRw6‐ and 8‐ associated HLA‐Dw HAG specificity defined by homozygous typing cell 9W 1802

Cloned human T lymphocytes with lymphostimulatory capacity preferentially activate suppressor cells

Function of alloproliferative T lymphocyte clones correlates better with their class II recognitive specificity than with their cell surface phenotype

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