scholarly journals Mice whose B cells cannot produce the T15 idiotype also lack an antigen-specific helper T cell required for T15 expression.

1979 ◽  
Vol 150 (6) ◽  
pp. 1399-1409 ◽  
Author(s):  
K Bottomly ◽  
D E Mosier
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Antibody Response ◽  
Cell Function ◽  
Cell Subset ◽  
Helper T Cells ◽  
Helper T Cell ◽  
T Cell Subset ◽  
Male Donor

The X-linked CBA/N defect in B cell function precludes an antibody response to phosphorylcholine (PC). Accordingly, (CBA/N X BALB/c)F1 male mice are unresponsive to PC and lack circulating immunoglobulin bearing the T15 idiotype characteristic of BALB/C anti-PC antibody. In contrast, (CBA/N X BALB/c)F1 female mice respond to PC and greater than 80% of the anti-PC antibody is T15+. No T-cell abnormalities are known to be associated with the CBA/N mutation. These experiments compared the ability of helper T cells from either (CBA/N X BALB/c)F1 male (T15-) or F1 female (T15+) mice to help F1 female B cells respond to PC and to influence the level of T15 expression. The results indicate that although F1 male T cells collaborated with F1 female B cells just as efficiently as F1 female T cells for the total anti-PC response, the percentage of T15 expression induced by F1 male T cells fell dramatically. The (CBA/N X BALB/c)F1 male thus appear to lack a helper T-cell subset required for dominant idiotype production. This helper T cell defect could be repaired by adding F1 female T cells primed to a second carrier to F1 male T cells and restimulating the cell mixture with PC coupled to the antigen used to prime the F1 male cells plus free second carrier. This result implies that conventional helper T cells derived from the F1 male donor can collaborate with a distinct helper T-cell subset from the F1 female donor which recognizes both carrier and idiotype to induce an anti-PC antibody response dominated by the T15 clonotype.

scholarly journals The role of H-2 linked genes in helper T-cell function. IV. Importance of T-cell genotype and host environment in I-region and Ir gene expression.

1978 ◽  
Vol 148 (6) ◽  
pp. 1510-1522 ◽  
Author(s):  
J W Kappler ◽  
P Marrack
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Cell Function ◽  
High Responder ◽  
Helper T Cells ◽  
Helper T Cell ◽  
Region Gene ◽  
Host Environment ◽  
Low Responder

We have studied the properties of helper T cells specific for sheep erythrocytes (SRBC), keyhole limpet hemocyanin (KLH), or poly-L-(Tyr,Glu)-poly-DL-Ala-poly-L-Lys [(T,G)-A--L]. These T cells differentiated and were primed in vivo in irradiation chimeras constructed of various combinations of F1 and parental bone marrow donors and irradiated recipients. Primed T cells were then tested for helper activity in the in vitro response of B cells and macrophages (Mphi) of parental or F1 origin to the hapten trinitrophenol coupled to the priming antigen. When testing either SRBC or KLH-specific T cells of parental H-2 type which had differentiated in F1 hosts, we found that they cooperated equally well with B cells and Mphi of either parental H-2 type. On the other hand, when testing F1 T cells which had differentiated in parental hosts, we found that they cooperated well only with B cells and Mphi which had the K-IA region type of the parental host. In similar experiments we found that (T,G)-A--L-specific T cells of low responder H-2 type which had differentiated in (high responder X low responder) F1 hosts induced high responses in high responder B cells and Mphi (T,G)-A--L-specific F1 T cells which differentiated in high responder but not those which differentiated in low responder hosts induced high responses in high responder B cells and Mphi. Low responder B cells and Mphi yielded low responses in all cases regardless of the source of (T,G)-A--L-specific T cells with what they were tested. Our results support the conclusion that I-region and Ir genes function via their expression in B cells and Mphi and in the host environment during helper T-cell differentiation, but not, at least under the conditions of these experiments, via their expression in the helper T cell itself. These findings place constraints upon models which attempt to explain the apparent dual recognition of antigen and I-region gene products by helper T cells.

scholarly journals Mechanisms regulating IgA class-specific immunoglobulin production in murine gut-associated lymphoid tissues. II. Terminal differentiation of postswitch sIgA-bearing Peyer's patch B cells.

1983 ◽  
Vol 158 (3) ◽  
pp. 649-669 ◽  
Author(s):  
H Kawanishi ◽  
L Saltzman ◽  
W Strober
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Present Report ◽  
Protein A ◽  
Cell Subset ◽  
Terminal Differentiation ◽  
Lymphoid Tissues ◽  
T Cell Subset ◽  
Iga Production

Our previous studies indicated that cloned T cells obtained from Peyer's patches (PP) (Lyt-1+, 2-, Ia+, and H-2K/D+) evoked immunoglobulin (Ig) class switching of PP B cells from sIgM to sIgA cells in vitro; however, these switch T cells could not in themselves provide optimal help for the differentiation of postswitch sIgA-bearing PP B cells to IgA-secreting cells. Thus, in the present report we described studies focused on mechanisms regulating terminal differentiation of the postswitch PP sIgA-bearing B cells. First, to explore the effect of T cell-derived B cell differentiation factor(s) (BCDF) and macrophage factor(s) (MF) on the terminal maturation of PP B cells, LPS-stimulated PP B cells were co-cultured for 7 d with cloned T cells in the presence or absence of the above factors. In the absence of PP cloned T cells the BCDF and MF had only a modest effect on IgA production, whereas in the presence of PP, but not spleen cloned T cells, IgA production was increased. Next, to investigate the effect of T cells derived from a gut-associated lymphoid tissue (GALT), mesenteric lymph nodes (MLN), as well as from spleen on terminal differentiation of postswitch sIgA PP B cells, LPS-driven PP B cells were precultured with the cloned T cells to induce a switch to sIgA, and subsequently cultured with MLN or spleen T cells or a Lyt-2+-depleted T cell subset in the presence of a T-dependent polyclonal mitogen, staphylococcal protein A. Alternatively, in the second culture period BCDF alone was added, instead of T cells and protein A. Here it was found that B cells pre-exposed to switch T cells from PP, but not spleen, were induced to produce greatly increased amounts of IgA in the presence of protein A and T cells or a Lyt-2+-depleted T cell subset as well as in the presence of BCDF alone. Furthermore, in the presence of BCDF alone many B cells expressed cytoplasmic IgA. These observations strongly support the view that the terminal differentiation of postswitch sIgA B cells is governed by helper T cells and macrophages, or factors derived from such cells. Such cells or factors do not affect preswitch B cells.

scholarly journals The role of H-2-linked genes in helper T cell function. VII. Expression of I region and immune response genes by B cells in bystander help assays.

1980 ◽  
Vol 152 (5) ◽  
pp. 1274-1288 ◽  
Author(s):  
P Marrack ◽  
J W Kappler
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Function ◽  
High Responder ◽  
Helper T Cells ◽  
Spleen Cells ◽  
Region Gene ◽  
Immunoglobulin Receptor

The mode of action by bystander helper T cells was investigated by priming (responder X nonresponder) (B6A)F1 T cells with poly-L-(Tyr, Glu)-poly-D,L-Ala--poly-L-Lys [(TG)-A--L] and titrating the ability of these cells to stimulate an anti-sheep red blood cell (SRBC) response of parental B cells and macrophages in the presence of (TG)-A--L. Under limiting T cell conditions, and in the presence of (TG)-A--L, (TG)-A--L-responsive T cells were able to drive anti-SRBC responses of high-responder C57BL/10.SgSn (B10) B cells and macrophages (M0), but not of low-responder (B10.A) B cells and M0. Surprisingly, the (TG)-A--L-driven anti-SRBC response of B10.A B cells was not restored by addition of high-responder acessory cells, in the form of (B6A)F1 peritoneal or irradiated T cell-depleted spleen cells, or in the form of B10 nonirradiated T cell-depleted spleen cells. These results suggested that (TG)-A--L-specific Ir genes expressed by B cells controlled the ability of these cells to be induced to respond to SRBC by (TG)-A--L-responding T cells, implying that direct contact between the SRBC-binding B cell precursor and the (TG)-A--L-responsive helper T cells was required. Analogous results were obtained for keyhold limpet hemocyanin (KLH)-driven bystander help using KLH-primed F1 T cells restricted to interact with cells on only one of the parental haplotypes by maturing them in parental bone marrow chimeras. It was hypothesized that bystander help was mediated by nonspecific uptake of antigen [(TG)-A--L or KLH] by SRBC-specific b cells and subsequent display of the antigen on the B cell surface in association with Ir of I-region gene products, in a fashion similar to the M0, where it was then recognized by helper T cells. Such an explanation was supported by the observation that high concentrations of antigen were required to elicit bystander help. This hypothesis raises the possibility of B cell processing of antigen bound to its immunoglobulin receptor and subsequent presentation of antigen to helper T cells.

Thymomas alter the T-cell subset composition in the blood: a potential mechanism for thymoma-associated autoimmune disease

Blood ◽  
2000 ◽  
Vol 96 (12) ◽  
pp. 3872-3879 ◽  
Author(s):  
Viola Hoffacker ◽  
Anja Schultz ◽  
James J. Tiesinga ◽  
Ralf Gold ◽  
Berthold Schalke ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Autoimmune Disease ◽  
Cd8 T Cells ◽  
Cell Function ◽  
Cell Subset ◽  
Cell Repertoire ◽  
T Cell Subset ◽  
Functional Studies ◽  
Circulating T Cells

Abstract Thymomas are the only tumors that are proven to generate mature T cells from immature precursors. It is unknown, however, whether intratumorous thymopoiesis has an impact on the peripheral T-cell pool and might thus be related to the high frequency of thymoma-associated myasthenia gravis. This study shows, using fluorescence-activated cell sorting-based analyses and T-cell proliferation assays, that thymopoiesis and T-cell function in thymomas correspond with immunologic alterations in the blood. Specifically, the proportion of circulating CD45RA+CD8+ T cells is significantly increased in patients with thymoma compared with normal controls, in accordance with intratumorous T-cell development that is abnormally skewed toward the CD8+ phenotype. Moreover, it is primarily the proportion of circulating CD45RA+CD8+ T cells that decreases after thymectomy. The results also demonstrate that T cells reactive toward recombinant autoantigens are distributed equally between thymomas and blood, whereas T-cell responses to foreign antigen (ie, tetanus toxoid) are seen only among circulating T cells and not among thymoma-derived T cells. These functional studies support the hypothesis that thymopoiesis occurring within thymomas alters the peripheral T-cell repertoire. Because many thymomas are enriched with autoantigen-specific T cells, a disturbance of circulating T-cell subset composition by export of intratumorous T cells may contribute to paraneoplastic autoimmune disease arising in patients with thymoma.

scholarly journals Anti-idiotype induced regulation of helper cell function for the response to phosphorylcholine in adult BALB/c mice.

1978 ◽  
Vol 148 (5) ◽  
pp. 1216-1227 ◽  
Author(s):  
K Bottomly ◽  
B J Mathieson ◽  
D E Mosier
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Antibody Response ◽  
Gamma Globulin ◽  
Cell Function ◽  
Keyhole Limpet Hemocyanin ◽  
Secondary Antibody ◽  
Suppressor T Cells ◽  
Helper Activity

An adoptive secondary antibody response to phosphorylcholine (PC) can be generated by the transfer of keyhole limpet hemocyanin (KLH)-primed T cells, PC-bovine gamma globulin-primed B cells, and PC-KLH into irradiated syngeneic BALB/c mice. If the KLH-primed T-cell donors were pretreated with anti-idiotype antibodies directed against the BALB/c PC-binding myeloma TEPC 15, their T cells were unable to collaborate effectively with PC-primed B cells; moreover, they could suppress the helper activity of T cells from normal mice for the PC-KLH response. The Ly phenotype of these T cells was found to be Ly 1-, 2+. The specificity of the suppressor T-cell population induced by anti-T15 treatment appears to be both for idiotype (hapten) and carrier, since the suppressor T cells fail to interfere with the antibody response to PC on a heterologous carrier, nor do they suppress the response to trinitrophenol-KLH.

scholarly journals Cellular and genetic control of antibody responses. V. Helper T-cell recognition of H-2 determinants on accessory cells but not B cells.

1979 ◽  
Vol 149 (5) ◽  
pp. 1208-1226 ◽  
Author(s):  
A Singer ◽  
K S Hathcock ◽  
R J Hodes
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Helper T Cells ◽  
Cell Recognition ◽  
Helper T Cell ◽  
T Cell Recognition ◽  
Accessory Cells

Requirements for helper T-cell recognition of H-2 determinants expressed on adherent accessory cells and on B cells was individually assessed in the anti-hapten PFC responses to TNP-KLH. Complicating allogeneic effects were minimized or avoided by the use of helper T cells from normal F1 hybrids, parent leads to F1 chimeras, and F1 leads to parent chimeras. The results of both in vitro and in vivo experiments demonstrated that: (a) helper T cells are not required to recognize the identical H-2 determinants on both accessory cells and B cells; (b) helper T cells are required to recognize K or I-A region-encoded determinants expressed on accessory cells; (c) no requirement was observed in vitro or in vivo for helper T-cell recognition of B-cell-expressed H-2 determinants; and (d) no requirement was observed for H-2 homology between accessory cells and B cells. The absence of required helper T-cell recognition of the identical H-2 determinants on both accessory cells and B cells was demonstrated in two ways: (a) naive of KLH-primed (A x B)F1 hybrid helper T cells collaborated equally well with B cells from either parentA or parentB in the presence of accessory cells from either parent; (b) A leads to (A x B)F1 chimeric spleen cells depleted of accessory cells collaborated equally well with accessory cells from either parentA or parentB, even though the B cells only expressed the H-2 determinants of parentA. A requirement for helper T-cell recognition of K or I-A region-encoded H-2 determinants on accessory cells was also demonstrated in two ways: (a) (A x B)F1 leads to parentA chimeric spleen cells depleted of accessory cells collaborated with accessory cells from parentA but not parentB; and (b) (A x B)F1 leads to parentA chimeric helper T cells collaborated with normal F1 B cells only in the presence of parental or recombinant accessory cells that expressed the K or I-A region-encoded determinants of parentA. Although restricted in their ability to recognize H-2 determinants on accessory cells, it was demonstrated both in vitro and in vivo that (A x B)F1 leads to parentA chimeric helper T cells were able to collaborate with B cells from either parentA or parentB. In vitro in the presence of accessory cells from parentA, (A x B)F1 leads to parentA chimeric helper T cells collaborated equally well with B cells from either parent. In addition, the inability of (A x B)F1 leads to parentA chimeric helper T cells to collaborate with (B + accessory) cells from parentB was successfully reversed by the addition of parentA SAC as added accessory cells. In vivo, upon the addition of parentA accessory cells, (A x B)F1 leads to parentA chimeric helper T cells collaborated with parentB B cells in short-term adoptive transfer experiments.

scholarly journals The role of H-2-linked genes in helper T-cell function. I. In vitro expression in B cells of immune response genes controlling helper T-cell activity

1977 ◽  
Vol 146 (6) ◽  
pp. 1748-1764 ◽  
Author(s):  
JW Kappler ◽  
P Marrack
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cross Reaction ◽  
Helper T Cells ◽  
Helper T Cell ◽  
Low Responder ◽  
The Cross

The ability of murine helper T cells primed to the antigen, sheep erythrocytes (SRBC) to cross-react with burro erythrocytes (BRBC) in the in vitro anti-trinitrophenol (TNP) response to TNP-RBC was shown to be under genetic control. Although non-H-2 genes were shown to influence the absolute level of helper activity assayed after SRBC priming, the extent of cross-reaction of SRBC-primed helpers with BRBC was shown to be controlled by an H-2-1inked Ir gene(s). H-2 haplotypes were identified which determined high, intermediate, or low response to the cross- reacting determinants and the gene(s) controlling the cross-reaction tentatively mapped to the K through I-E end of the H-2 complex. Helpers primed in F(1) mice of high x intermediate or high x low responder parents were tested for cross-reaction using B cells and macrophages (Mφ) of parental haplotypes. In each case the extent of cross-reaction was predicted by the H-2 haplotype of the B cells and Mφ, establishing the expression of the Ir gene(s) in B cells and/or Mφ a t least, but not ruling out its expression in T cells as well. The low cross-reaction seen when T cells from F(1) mice of high × low responder parents were tested on low responder B cells and Mφ was not increased by the presence of high responder Mφ, indicating the Ir gene(s) is expressed in the B cell a t least although it may be expressed in Mφ as well. These and our previously reported experiments are consistent with the hypothesis that helper T cells recognize antigen bound to the surface of B cells and Mφ in association with the product(s) of Ir gene(s) expressed on the B cell and Mφ.

scholarly journals Two distinct types of helper T cells involved in the secondary antibody response: independent and synergistic effects of Ia- and Ia+ helper T cells.

1978 ◽  
Vol 147 (2) ◽  
pp. 446-458 ◽  
Author(s):  
T Tada ◽  
T Takemori ◽  
K Okumura ◽  
M Nonaka ◽  
T Tokuhisa
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Response ◽  
Helper T Cells ◽  
Helper T Cell ◽  
Ia Antigen ◽  
Nylon Wool ◽  
B Cell Response

We have described here two distinct types of carrier-specific helper T cells which act independently and synergistically to augment the B-cell response to a hapten. They are separable by passage through a nylon wool column. The first type of helper T cell, which we designate as Th1, is nylon nonadherent, and can help the response of hapten-primed B cells only if the haptenic and carrier determinants are present on a single molecule (cognate interaction). The second type of helper T cell, Th2, adheres to the nylon wool column, and can help the B-cell response to a hapten coupled to a heterologous carrier upon stimulation with unconjugated relevant carrier (polyclonal interaction). The addition of a small number of Th2 to the mixture of Th1 and B cells significantly augmented the net response to the hapten carrier conjugate. Both Th1 and Th2 cells belong to the Lyt-1+,2-,3- subclass. Th1 has no detectable Ia antigen, whereas Th2 is killed by certain anti-Ia antisera and complement. The Ia antigen detected on Th2 was found to be controlled by a locus in the I-J subregion. The results clearly established the fact that there are two distinct pathways in the T- and B-cell collaboration, which involves two different subsets of carrier-specific helper T cells.

scholarly journals Helper and suppressor T-cell function in HIV-infected hemophilia patients

Blood ◽  
1989 ◽  
Vol 74 (1) ◽  
pp. 298-302 ◽  
Author(s):  
R Weimer ◽  
T Schweighoffer ◽  
K Schimpf ◽  
G Opelz
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Function ◽  
Cell Subset ◽  
Pokeweed Mitogen ◽  
Suppressor Activity ◽  
T Cell Subset ◽  
Group 3 ◽  
Group 2 ◽  
Hiv Negative

Abstract T-lymphocyte helper and suppressor functions were assessed in 61 hemophilia patients. Twenty one patients were HIV-negative (Group 1), 27 were HIV-positive without having AIDS-related complex (ARC)/AIDS (Group 2), and 13 had ARC/AIDS (Group 3). T, CD4-positive, or CD8- positive T lymphocytes were cocultured with B lymphocytes and pokeweed mitogen for 6 days and immunoglobulin producing cells were assessed in a reverse hemolytic plaque assay. In HIV-infected patients, T cells as well as the CD4-positive T cell subset exhibited reduced helper (P less than .01, Group 2; P less than .0005, Group 3) and elevated suppressor activity (P less than .02, Group 2; P less than .005, Group 3), whereas no significant difference was found between HIV-negative patients and controls. The number of CD4-positive cells was not correlated with CD4 cell function. CD4-positive cells showed no helper activity (less than 10% of control T cells) in 8/11 (73%), but an excessive suppressor activity (greater than 80% suppression of plaque formation) in 6/11 (55%) Group 3 patients. Our results show that defective helper and elevated suppressor functions of T cells in HIV-infected patients are caused not only by a change in the CD4/CD8 cell counts but also by functional abnormalities of the CD4-positive T-cell subset. These abnormal helper and suppressor functions may play a role in the development of the immunodeficiency state of AIDS patients.

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