scholarly journals MIXED LYMPHOCYTE REACTIVITY AGAINST NORMAL CELLS BY SPLENIC LYMPHOCYTES FROM TUMOR-BEARING MICE

1974 ◽  
Vol 139 (1) ◽  
pp. 224-229 ◽  
Author(s):  
R. G. Devlin ◽  
J. D. McCurdy ◽  
P. E. Baronowsky
Keyword(s):  
Parental Strain ◽  
Mixed Lymphocyte Culture ◽  
Lymphocyte Culture ◽  
Spleen Cells ◽  
Tumor Bearing ◽  
Normal Spleen ◽  
Immune Attack ◽  
Transplantable Leukemia ◽  
Cellular Immune ◽  
Lymphocyte Reactivity

The establishment of an intimate connection between autoimmunity and neoplasia would require the demonstration of an experimentally induced, tumor-dependent autoimmune process. For this reason, we have studied cellular immune reactions of mice bearing a transplantable leukemia (L1210). Spleen cells from hybrid BDF1 mice bearing the L1210 tumor (BDFt) reacted vigorously in mixed lymphocyte culture with mitomycin-treated, normal spleen cells from mice of the parental strain from which the L1210 tumor was derived (DBA/2). Spleen cells from nontumor-bearing BDF1 mice reacted only weakly with these parental cells. The BDFt cells likewise did not respond when cultured with mitomycin-treated spleen cells from the other parental strain (C57B1/6). The vigorous mixed lymphocyte reaction (MLR) by BDFt cells against normal parental cells of the same strain as the tumor was not due to a double exposure of the reacting cells to histocompatibility antigens shared by tumor cells and normal parental cells. The response of cells from tumor-bearing F1 mice against normal parental cells seen in these experiments suggests the possibility of the induction of an autoimmune-like process against host lymphocytes by spleen cells from leukemic mice. Theoretically such a phenomenon would considerably reduce an animal's ability to mount an immune attack against malignant cells.

scholarly journals SYNERGY BETWEEN SUBPOPULATIONS OF MOUSE SPLEEN CELLS IN THE IN VITRO GENERATION OF CELL-MEDIATED CYTOTOXICITY

1974 ◽  
Vol 140 (6) ◽  
pp. 1646-1659 ◽  
Author(s):  
Richard J. Hodes ◽  
Barry S. Handwerger ◽  
William D. Terry
Keyword(s):  
Mixed Lymphocyte Culture ◽  
Lymphocyte Culture ◽  
Specific Cell ◽  
Spleen Cells ◽  
Normal Spleen ◽  
In Vitro Induction ◽  
Cytotoxic Effector ◽  
Nylon Wool

Two subpopulations separated from normal spleen have been shown to synergize as responding cells in the in vitro induction of specific cell-mediated cytotoxicity during the mixed lymphocyte culture (MLC). The synergizing populations are a nylon wool column-adherent and a nylon wool column-nonadherent fraction, enriched for B lymphocytes and T lymphocytes, respectively. When a mixture of these fractions is used as the responding cell population in MLC, greater cytotoxicity is generated than would be expected from the sum of activities generated in the two subpopulations sensitized separately. The synergy appears to occur at the sensitization rather than the effector phase. The synergizing cell which is contained in the nylon-adherent subpopulation is distinct from the cytotoxic effector T lymphocyte, is resistant to lysis by rabbit antimouse brain serum, and is unresponsive to phytohemagglutinin; its synergizing function could not be replaced by either plastic-adherent spleen cells or peritoneal exudate cells. These results suggest a role of a non-T-cell nonmacrophage population in the generation of cytotoxic activity.

scholarly journals MIXED LYMPHOCYTE REACTIVITY AGAINST NORMAL CELLS BY SPLENIC LYMPHOCYTES FROM TUMOR-BEARING MICE

1974 ◽  
Vol 139 (1) ◽  
pp. 230-237 ◽  
Author(s):  
R. G. Devlin ◽  
J. D. McCurdy ◽  
P. E. Baronowsky
Keyword(s):  
Lymphocytic Leukemia ◽  
Spleen Cells ◽  
Normal Cells ◽  
Tumor Bearing ◽  
Transplantable Tumors ◽  
Cellular Immune Responsiveness ◽  
Cellular Immune ◽  
Autoimmune Reactivity ◽  
The Relationship ◽  
Lymphocyte Reactivity

A possible consequence of an antilymphocytic autoimmune process would be serious impairment of an animal's ability to destroy tumor cells. One measure of autoimmune reactivity of this type would be the demonstration of cellular immune responsiveness by cells from tumor-bearing mice against syngeneic normal cells. These experiments demonstrate that spleen cells from mice bearing a lymphocytic leukemia of identical histocompatability type as the host mounted a vigorous immune response against normal syngeneic cells in a mixed lymphocyte reaction (MLR). Moreover, ascitic cells from leukemic mice responded significantly to normal syngeneic spleen cells in MLR's. The former reactions are usually much more vigorous than the responses of normal to malignant cells. These results are discussed in terms of the relationship between autoimmunity and neoplasia. Alternative explanations necessitated by the dangers involved in the interpretation of the immunology of transplantable tumors are considered.

scholarly journals Haplotype-specific suppression of cytotoxic T cell induction by antigen inappropriately presented on T cells.

1983 ◽  
Vol 157 (1) ◽  
pp. 141-154 ◽  
Author(s):  
P J Fink ◽  
I L Weissman ◽  
M J Bevan
Keyword(s):  
T Cells ◽  
Cytotoxic T Lymphocyte ◽  
Mixed Lymphocyte Culture ◽  
Lymphocyte Culture ◽  
Cytotoxic T Cell ◽  
Spleen Cells ◽  
Specific Suppression ◽  
Veto Cells

To detect a strong cytotoxic T lymphocyte (CTL) response to minor histocompatibility (H) antigens in a 5-d mixed lymphocyte culture, it is necessary to use a responder that has been primed in vivo with antigen-bearing cells. It has previously been shown that minor-H-specific CTL can be primed in vivo both directly by foreign spleen cells and by presentation of foreign minor H antigens on host antigen-presenting cells. This latter route is evident in the phenomenon of cross-priming, in which H-2 heterozygous (A x B)F1 mice injected 2 wk previously with minor H-different H-2A (A') spleen cells generate both H-2A- and H-2B-restricted minor-H-specific CTL. In a study of the kinetics of direct- vs. cross-priming to minors in F1 mice, we have found that minor H-different T cells actually suppress the induction of virgin CTL capable of recognizing them. CTL activity measured from F1 mice 3-6 d after injection with viable A' spleen cells is largely H-2B restricted. The H-2A-restricted response recovers such that roughly equal A- and B-restricted activity is detected in mice as early as 8-10 d postinjection. This temporary hyporeactivity does not result from generalized immunosuppression--it is specific for those CTL that recognize the foreign minor H antigen in the context of the H-2 antigens on the injected spleen cells. The injected spleen cells that mediate this suppression are radiosensitive T cells; Lyt-2+ T cells are highly efficient at suppressing the induction of CTL in vivo. No graft vs. host reaction by the injected T cells appears to be required, as suppression of direct primed CTL can be mediated by spleen cells that are wholly tolerant of both host H-2 and minor H antigens. Suppression cannot be demonstrated by in vitro mixing experiments. Several possible mechanisms for haplotype-specific suppression are discussed, including inactivation of responding CTL by veto cells and in vivo sequestration of responding CTL by the injected spleen cells.

scholarly journals Study of the cells proliferating in parent versus F hybrid mixed lymphocyte culture.

1975 ◽  
Vol 141 (4) ◽  
pp. 775-787 ◽  
Author(s):  
P F Piguet ◽  
H K Dewey ◽  
P Vassalli
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Lymphocytes ◽  
Hybrid Cell ◽  
Mixed Lymphocyte Culture ◽  
Lymphocyte Culture ◽  
Lymphoid Cells ◽  
Spleen Cells ◽  
F1 Hybrid ◽  
Proliferation And Differentiation

Caryotypic analysis of the cells dividing in mouse parent-hybrid MLC showed an F1 hybrid cell proliferation, which varied depending upon the source of lymphoid cells used: strong in spleen MLC (sometimes equal to that of the parental cells), less marked in lymph node cell MLC, and most often absent in MLC between cortisone-resistant (CR) thymocytes. MLC between parental spleen cells and F1 CR thymocytes showed, however, that in certain conditions of culture F thymocytes can also proliferate. Using parental or F1 spleen cells lacking T lymphocytes, it was found that F1 cell proliferation is entirely dependent upon the presence of parental T cells, but does not require the presence of T lymphocytes among the F1 cells. Immunofluorescence analysis of the blasts observed in one-way MLC showed that about 70% of the parental blasts were T blasts, and 25%B blasts (containing a high proportion of plasmablasts); among the F1 blasts, there was also the same percentage of B blasts and plasmablasts, but many of the T blasts bore only small amounts of T-cell antigen (MTLA), and there was also about 20%of unstained blasts, possibly T blasts bearing MTLA in amounts undetectable by immunofluorescence. The possibility is discussed that the F1 responding T cells belong to a subpopulation performing a suppressive function; MLC lacking F1 T cells showed increased [3H] thymidine incorporation. The proliferation and differentiation of parental and F1 B cells may result mainly from an unspecific, "polyclonal" triggering.

Mixed lymphocyte reactivity in spleen cells from F-9 tumor-bearing mice

1981 ◽  
Vol 62 (2) ◽  
pp. 334-340 ◽  
Author(s):  
Jeffrey A. Bluestone ◽  
Carlos Lopez ◽  
Ursula Hurtenbach
Keyword(s):  
Spleen Cells ◽  
Tumor Bearing ◽  
Lymphocyte Reactivity

scholarly journals CELL-MEDIATED LYMPHOLYSIS

1973 ◽  
Vol 137 (5) ◽  
pp. 1303-1309 ◽  
Author(s):  
Barbara J. Alter ◽  
Dolores J. Schendel ◽  
Marilyn L. Bach ◽  
Fritz H. Bach ◽  
Jan Klein ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Target Cell ◽  
Effector Cell ◽  
Mixed Lymphocyte Culture ◽  
Lymphocyte Culture ◽  
Mouse Spleen ◽  
Spleen Cells ◽  
Histocompatibility Complex ◽  
Region Difference ◽  
Mediate Cell

The cell-mediated lympholytic capability of mouse spleen cells stimulated in mixed lymphocyte culture is related to the major histocompatibility complex genotype on target lymphocytes. The strain combinations AQR-B10. T(6R) and B10.A(4R)-B10.A(2R) that result in significant mixed lymphocyte culture activation do not mediate cell-mediated lympholysis on sensitizing target lymphocytes; serologically defined regions (H-2K and H-2D) are identical within each combination. H-2K or H-2D region disparity alone does not cause cell-mediated lympholysis. However after mixed lymphocyte culture activation as seen with B10.A-B10.T(6R), a target cell bearing only an H-2K region difference from the effector cell is sensitive to cell-mediated lympholysis. Likewise an H-2D region difference is an adequate target after mixed lymphocyte culture activation of the effector cell in the combination B10.A(2R)-B10.D2.

scholarly journals Evidence that Lyb-2 is critical to specific activation of B cells before they become responsive to T cell and other signals.

1982 ◽  
Vol 155 (5) ◽  
pp. 1309-1316 ◽  
Author(s):  
H Yakura ◽  
F W Shen ◽  
E Bourcet ◽  
E A Boyse
Keyword(s):  
B Cells ◽  
Sheep Erythrocyte ◽  
Mixed Lymphocyte Culture ◽  
Lymphocyte Culture ◽  
Cell Surface Molecules ◽  
Subsequent Generation ◽  
Spleen Cells ◽  
Soluble Factors ◽  
Surface Molecules

The generation of plaque-forming cells (PFC) to T-dependent antigen, but not to T-independent antigen, is reduced in vitro by Lyb-2 antibody. Monoclonal Lyb-2 antibody, added to Mishell-Dutton cultures within the first 2 d, but not later, greatly reduces the generation of alpha-sheep erythrocyte (SRBC) PFC from T-depleted spleen cells whether help is provided in the form of intact T cells or as soluble factors contained in mixed lymphocyte culture (MLC) supernatants. Generation of alpha-SRBC PFC from purified B cells, assisted by soluble factors in MLC and macrophage (P388D.1 cell) supernatants, is similarly reduced by Lyb-2 antibody. The initial 2-d period, during which cultures are diminishingly sensitive to reduction of PFC generation by Lyb-2 antibody, is not affected by the time at which such soluble factors are added. Thus, Lyb-2 cell surface molecules evidently do not function as receptors for these differentiative signals. Reduction of PFC generation by Lyb-2 antibody is antigen dependent in the sense that reduction of the PFC response to one antigen (SRBC) does not affect subsequent generation of PFC to a second antigen (horse erythrocytes) from the same cell population. These findings accord with the view that the Lyb-2 molecule participates in a B cell differentiative phase, probably proliferative, which begins with binding of antigen and precedes the phase in which B cells become fully receptive to signals from T and other cells.

scholarly journals Lymphocyte reactivity in rheumatoid arthritis. Mixed lymphocyte culture.

1975 ◽  
Vol 34 (3) ◽  
pp. 231-234 ◽  
Author(s):  
E M Caperton ◽  
D R Baker ◽  
R A King
Keyword(s):  
Rheumatoid Arthritis ◽  
Mixed Lymphocyte Culture ◽  
Lymphocyte Culture ◽  
Lymphocyte Reactivity

scholarly journals The effect of allogeneic presensitization on H-Y graft survival and in vitro cell-mediated responses to H-y antigen.

1976 ◽  
Vol 144 (3) ◽  
pp. 810-820 ◽  
Author(s):  
R D Gordon ◽  
B J Mathieson ◽  
L E Samelson ◽  
E A Boyse ◽  
E Simpson
Keyword(s):  
Mixed Lymphocyte Culture ◽  
Lymphocyte Culture ◽  
The Other ◽  
Target Cells ◽  
Spleen Cells ◽  
Cytotoxic Cells ◽  
Parental Haplotype ◽  
Cytotoxic Responses

C57BL/6 and C57BL/10 female mice were grafted with skin from male or female donors incompatible for H-2 and/or non-H-2 antigens. Syngeneic male grafts applied after the rejection of primary allografts or syngeneic male grafts were rejected in accelerated (second set) fashion, whereas male grafts applied after primary female grafts were not. In addition, C57BL/10 female spleen cells, primed in vivo with an allogeneic (BALB/c, CBA, or B10.BR) male graft and challenged in vitro in mixed lymphocyte culture with syngeneic (C57BL/10) male cells, produced cytotoxic cells specific for syngeneic male target cells. We conclude that at least some component of H-Y is detected by female responder cells on allogeneic male cells, and that the second set cell mediated response to H-Y is not necessarily restricted by the H-2 haplotype of the primary sensitizing strain. Moreover, (CBA X B10) F1 females, primed in vivo with male cells of one parental haplotype (B10 or CBA) and challenged in vitro with male cells of the other parental haplotype (CBA or B10), fail to lyse male target cells of either parental haplotype. It therefore seems unlikely that a helper determinant shared between B10 and CBA is sufficient to explain the ability of CBA male cells to prime H-2-restricted T-cell cytotoxic responses by B10 females.

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