Abstract
The in vivo effects of intravenous administration of alloantisera directed to I-J subregion coded determinants were investigated. In confirmation and extension of our previous results, anti-I-Jk [B10.A(3R) anti-B10.A(5R)] and anti-I-Js ([B10.A(3R) X B10.S(9R)]F1 anti-B10.HTT) antisera, when administered in 1 to 10 microliter amounts at the time of immunization, led to twofold increases in the IgM and IgG plaque-forming cells (PFC) responses to suboptimal doses of sheep erythrocytes in A/J (I-Jk) and SJL (I-Js) mice, respectively. To assess whether this immunopotentiation was due to a decrease in specific suppression, experiments were carried out using the polypeptide antigens random linear terpolymer of L-glutamic acid60, L-alanine30, and L-tyrosine10 (GAT) and random linear copolymer of L-glutamic acid50- L-tyrosine50 (GT), since administration of GAT to the nonresponder strain SJL, or GT to the nonresponder strain CBA fails to induce a primary PFC response and stimulates specific suppressor T cells able to prevent PFC responses to subsequent challenge with the immunogens GAT- methylated bovine serum albumin (MBSA) or GT-MBSA, respectively. The current study demonstrates that CBA (I-Jk) mice given 100 microgram GT in Maalox-pertussis adjuvant on day 0, and 10 microliter anti-I-Jk antiserum i.v. on days 0, 1, and 2, develop a significant primary specific PFC response on day 7. A similar responsiveness to 10 microgram GAT is found in SJL mice treated with 10 microliter anti-I-Js antiserum for 3 days. This same active anti-I-Js antiserum does not permit CBA mice to respond to GT, demonstrating the specificity of the anti-I-J effect. These data suggest that anti-I-J antiserum treatment at the time of antigen administration reduces suppressor responses to GAT or GT, permitting primary PFC responses. To directly demonstrate such an effect on suppressor activity, SJL or CBA mice treated, respectively, with GAT or GT to induce suppressor cells active on GAT- MBSA or GT-MBSA responses after adoptive transfer to normal syngeneic recipients were also given anti-I-J antisera (10 microliter/day) for 3 days, at which time their spleen cells were tested for suppressive activity upon transfer. Cells from such treated mice failed to show detectable suppressive activity upon transfer to syngeneic recipients challenged with GAT-MBSA or GT-MBSA, confirming the hypothesis of an in vivo effect of anti-I-J antiserum on suppressor activity.
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- Askenase P. W., Hayden B. J., Gershon R. K. Augmentation of delayed-type hypersensitivity by doses of cyclophosphamide which do not affect antibody responses. J Exp Med. 1975 Mar 1;141(3):697–702. doi: 10.1084/jem.141.3.697. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Debré P., Kapp J. A., Benacerraf B. Genetic control of specific immune suppression. I. Experimental conditions for the stimulation of suppressor cells by the copolymer L-glutamic acid50-L-tyrosine50 (GT) in nonresponder BALB/c mice. J Exp Med. 1975 Dec 1;142(6):1436–1446. doi: 10.1084/jem.142.6.1436. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Debré P., Kapp J. A., Dorf M. E., Benacerraf B. Genetic control of specific immune suppression. II. H-2-linked dominant genetic control of immune suppression by the random copolymer L-glutamic acid50-L-tyrosine50 (GT). J Exp Med. 1975 Dec 1;142(6):1447–1454. doi: 10.1084/jem.142.6.1447. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Debré P., Waltenbaugh C., Dorf M. E., Benacerraf B. Genetic control of specific immune suppression. IV. Responsiveness to the random copolymer L-glutamic acid50-L-tyrosine50 induced in BALB/c mice by cyclophosphamide. J Exp Med. 1976 Jul 1;144(1):277–281. doi: 10.1084/jem.144.1.277. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Frelinger J. A., Niederhuber J. E., Shreffler D. C. Effects of anti-Ia sera on mitogenic responses. III. Mapping the genes controlling the expression of Ia determinants on concanavalin A-reactive cells to the I-J subregion of the H-2 gene complex. J Exp Med. 1976 Oct 1;144(4):1141–1146. doi: 10.1084/jem.144.4.1141. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Frelinger J. A., Niederhuber J. E., Shreffler D. C. Inhibition of immune responses in vitro by specific antiserums to Ia antigens. Science. 1975 Apr 18;188(4185):268–270. doi: 10.1126/science.1118728. [DOI] [PubMed] [Google Scholar]
- Fujimoto S., Greene M. I., Sehon A. H. Regualtion of the immune response to tumor antigens. I. Immunosuppressor cells in tumor-bearing hosts. J Immunol. 1976 Mar;116(3):791–799. [PubMed] [Google Scholar]
- Fujimoto S., Greene M. I., Sehon A. H. Regulation of the immune response to tumor antigens. II. The nature of immunosuppressor cells in tumor-bearing hosts. J Immunol. 1976 Mar;116(3):800–806. [PubMed] [Google Scholar]
- Germain R. N., Thèze J., Kapp J. A., Benacerraf B. Antigen-specific T-cell-mediated suppression. I. Induction of L-glutamic acid60-L-alanine30-L-tyrosine10 specific suppressor T cells in vitro requires both antigen-specific T-cell-suppressor factor and antigen. J Exp Med. 1978 Jan 1;147(1):123–136. doi: 10.1084/jem.147.1.123. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gershon R. K., Maurer P. H., Merryman C. F. A cellular basis for genetically controlled immunologic unresponsiveness in mice: tolerance induction in T-cells. Proc Natl Acad Sci U S A. 1973 Jan;70(1):250–254. doi: 10.1073/pnas.70.1.250. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Greene M. I., Pierres A., Dorf M. E., Benacerraf B. The I-J subregion codes for determinats on suppressor factor(s) which limit the contact sensitivity response to picryl chloride. J Exp Med. 1977 Jul 1;146(1):293–296. doi: 10.1084/jem.146.1.293. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Herzenberg L. A., Okumura K., Cantor H., Sato V. L., Shen F. W., Boyse E. A., Herzenberg L. A. T-cell regulation of antibody responses: demonstration of allotype-specific helper T cells and their specific removal by suppressor T cells. J Exp Med. 1976 Aug 1;144(2):330–344. doi: 10.1084/jem.144.2.330. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kapp J. A., Pierce C. W., Benacerraf B. Genetic control of immune responses in vitro. VI. Experimental conditions for the development of helper T-cell activity specific for the terpolymer L-glutamic aicd60-L-alanine30-L-tyrosine10 (GAT) in nonresponder mice. J Exp Med. 1975 Jul 1;142(1):50–60. doi: 10.1084/jem.142.1.50. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kapp J. A., Pierce C. W., Schlossman S., Benacerraf B. Genetic control of immune responses in vitro. V. Stimulation of suppressor T cells in nonresponder mice by the terpolymer L-glutamic acid 60-L-alanine 30-L-tyrosine 10 (GAT). J Exp Med. 1974 Sep 1;140(3):648–659. doi: 10.1084/jem.140.3.648. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Murphy D. B., Herzenberg L. A., Okumura K., Herzenberg L. A., McDevitt H. O. A new I subregion (I-J) marked by a locus (Ia-4) controlling surface determinants on suppressor T lymphocytes. J Exp Med. 1976 Sep 1;144(3):699–712. doi: 10.1084/jem.144.3.699. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Okuda K., David C. S., Shreffler D. C. The role of gene products of the I-J subregion in mixed lymphocyte reactions. J Exp Med. 1977 Dec 1;146(6):1561–1573. doi: 10.1084/jem.146.6.1561. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pierce C. W., Johnson B. M., Gershon H. E., Asofsky R. Immune responses in vitro. 3. Development of primary gamma-M, gamma-G, and gamma-A plaque-forming cell responses in mouse spleen cell cultures stimulated with heterologous erythrocytes. J Exp Med. 1971 Aug 1;134(2):395–416. doi: 10.1084/jem.134.2.395. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pierce C. W., Kapp J. A., Solliday S. M., Dorf M. E., Benacerraf B. Immune responses in vitro. XI. Suppression of primary IgM and IgG plaque-forming cell responses in vitro by alloantisera against leukocyte alloantigens. J Exp Med. 1974 Oct 1;140(4):921–938. doi: 10.1084/jem.140.4.921. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pierres M., Germain R. N., Dorf M. E., Benacerraf B. Potentiation of a primary in vivo antibody response by alloantisera against gene products of the I region of the H-2 complex. Proc Natl Acad Sci U S A. 1977 Sep;74(9):3975–3979. doi: 10.1073/pnas.74.9.3975. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tada T., Taniguchi M., David C. S. Properties of the antigen-specific suppressive T-cell factor in the regulation of antibody response of the mouse. IV. Special subregion assignment of the gene(s) that codes for the suppressive T-cell factor in the H-2 histocompatibility complex. J Exp Med. 1976 Sep 1;144(3):713–725. doi: 10.1084/jem.144.3.713. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tada T., Taniguchi M., David C. S. Suppressive and enhancing T-cell factors as I-region gene products: properties and the subregion assignment. Cold Spring Harb Symp Quant Biol. 1977;41(Pt 1):119–127. doi: 10.1101/sqb.1977.041.01.016. [DOI] [PubMed] [Google Scholar]
- Thèze J., Waltenbaugh C., Dorf M. E., Benacerraf B. Immunosuppressive factor(s) specific for L-glutamic acid50-L-tyrosine50 (GT) II. Presence of I-J determinants on the GT-suppressive factor. J Exp Med. 1977 Jul 1;146(1):287–292. doi: 10.1084/jem.146.1.287. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Waltenbaugh C., Thèze J., Kapp J. A., Benacerraf B. Immunosuppressive factor(s) specific for L-glutamic acid50-L-tyrosine50 (GT). III. Generation of suppressor T cells by a suppressive extract derived from GT-primed lymphoid cells. J Exp Med. 1977 Oct 1;146(4):970–985. doi: 10.1084/jem.146.4.970. [DOI] [PMC free article] [PubMed] [Google Scholar]