Cell Mediated Immunity: Separation of Cells Involved in Recognitive and Destructive Phases

Bach, Fritz H.; Segall, Miriam; Zier, Karen S.; Sondel, Paul M.; Alter, Barbara J.; Bach, Marilyn L.

doi:10.1126/science.180.4084.403

Cited by 211 publications

(71 citation statements)

References 21 publications

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“…(14C-thymidine uptake) and the amount of cytotoxicity (~Cr release) generated in the same culture well. Thus, at the level of response of a single CTL.P (a) all cultures showing cytotoxic activity also showed strong proliferative responses (stimulation indices 4.0), however, the amount of cytotoxicity varied for any given level of proliferation, and (b) some cultures showing good proliferative responses displayed no cytotoxic activity, a finding consistent with the conclusions of others that not all proliferating cells are killer cells (6,11). Table III compares the proliferative and cytotoxic responses at different dosages of C57BL/6 responding cells stimulated with an H-2 difference (BALB/c) or with an additional strong Mls locus difference (DBA/2).…”

Section: Development Of Cytotoxic Activity In Cultures With Low Numbesupporting

confidence: 73%

Histocompatibility antigen-activated cytotoxic T lymphocytes. II. Estimates of the frequency and specificity of precursors.

Lindahl

Wilson

1977

The Journal of Experimental Medicine

336

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Using limiting dilutions of responding cells in mouse mixed leukocyte cultures, we obtained direct estimates of the minimum frequency of precursors of cytotoxic T lymphocytes (CTL.P) for a variety of antigens. Depending on the strain combination, there were as many as 4-15 CTL.P reactive to DBA/2 among 10(4) lymph node cells. Taking into account that only 5-10% of peripheral T lymphocytes have the potential to develop into cytotoxic T lymphocytes (CTLs) (6), this implies that at least 1-2% of all CTL.P are responsive to any given H-2 haplotype difference. Precursors of cytotoxic cells thus have the same high frequency of cells reactive to alloantigens of the major histocompatibility complex as found among proliferating cells in graft-vs.-host reactions and mixed lymphocyte interactions. The frequencies of CTL.P reactive to xenoantigens (rat) or trinitrophenyl-modified self were less than half the frequency of alloreactive CTL.P. A minority of the CTL.P specific for one H-2 haplotype were also reactive to a third party H-2 haplotype, presumably on the basis of recognition of shared determinants. By dilution of sensitized cells from single microcultures, it was shown that a single CTL.P undergoes a minimum of three to four cell divisions and generates at least 8-16 CTLs after antigenic activation.

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Section: Development Of Cytotoxic Activity In Cultures With Low Numbesupporting

confidence: 73%

Histocompatibility antigen-activated cytotoxic T lymphocytes. II. Estimates of the frequency and specificity of precursors.

Lindahl

Wilson

1977

The Journal of Experimental Medicine

336

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“…Their data demonstrated that although suppressor T cells inhibited PFC responses only if present during the inductive phase of the response, suppression was not expressed until the later phase of exponential PFC proliferation. The development of primary cytotoxic lymphocyte responses in vitro is thought to require initial proliferation during the sensitizing MLR (35,36), although it is probable that the T-cell population responding in MLR is different from that which expresses cytotoxicity (37,38). Therefore, activated suppressor cell effects documented in studies of killer cell generation (8) may reflect suppression either of requisite proliferation in the sensitizing phase or of postproliferative differentiation of cytotoxic lymphocytes.…”

Section: Discussionmentioning

confidence: 99%

Regulatory Mechanisms in Cell-Mediated Immune Responses

Rich

1974

The Journal of Experimental Medicine

125

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Regulatory effects of alloantigen-activated thymus-derived lymphocytes in mixed lymphocyte reactions have been demonstrated. Mice were injected into foot pads with allogeneic spleen cells; 4 days following sensitization spleen or regional lymph node cells from these animals were treated with mitomycin C and incorporated into MLR as regulator populations syngeneic to the responder cell type. Activated spleen cells suppressed MLR responses 60–90% whereas activated lymph node cells from the same animals enhanced MLR responses. Suppression by activated spleen cells was not due to cytotoxic effects nor to altered kinetics of the proliferative response. Studies of splenic suppressor cell generation in vivo revealed peak activity four days after alloantigen stimulation with no activity demonstrable at 7 days or at later times. Suppressor cell activity was abrogated by treatment with anti-θC3H serum and complement, and was not alloantigen specific.

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“…This might lead to a decrease in the 19s response to new antigens as described by Baum and Ziff (37) for Brucella several years ago, and play a role in the increased incidence of infection. Bach and Bach (38) have recently demonstrated that recognition and killing may also be separate functions shared between T-cells in cell mediated immunity. Thus a defect here might also effect recognition of new antigens in delayed reactions.…”

Section: T-and B-lymphocytes In Ramentioning

confidence: 99%

Clinical aspects of T‐ and B‐lymphocytes in rheumatic diseases

Messner¹

1974

Arthritis & Rheumatism

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The recent increase in basic knowledge of thymic dependent (T-cell) and bone marrow dependent (B-cell) lymphocyte cooperation in the normal immune response has provided new and challenging concepts to apply to the study of rheumatic diseases. An excellent example of this approach is the theory proposed by Allison and his colleagues (1) suggesting how T and B lymphocytes might interact to produce autoantibodies.They postulate that in the normal response to thymus dependent foreign aiiti- gens a T-cell with anticarrier specificity recognizes the carrier portion of the antigen, and then cooperates with a B-cell which recognizes the hapten portion and produces antibody to the hapten. They also suggest that all normal individuals possess B-cells capable of recognizing self constituents and producing autoantibody; but that autoantibody is not made because T-cells do not recognize, or are tolerant, to self antigens. In this scheme, tolerance could be broken in several ways.For example, a virus attached to a self component, such as a cell, might be recognized by a T-cell specific for the virus. This T-cell could cooperate with a B-cell capable of recognizing self antigens on the cell surface. With the aid of this cooperation the B-cell could then produce antibody against the cell. In the case of an antigen attached to a self component, possibly an antigen attached to an antibody, the antigen might be recognized by a T-cell. This T-cell could then act as a helper cell for a B-cell which could recognize the carrier antibody. This B-cell could then make antibody to the antibody which we would

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Cell Mediated Immunity: Separation of Cells Involved in Recognitive and Destructive Phases

Cited by 211 publications

References 21 publications

Histocompatibility antigen-activated cytotoxic T lymphocytes. II. Estimates of the frequency and specificity of precursors.

Histocompatibility antigen-activated cytotoxic T lymphocytes. II. Estimates of the frequency and specificity of precursors.

Regulatory Mechanisms in Cell-Mediated Immune Responses

Clinical aspects of T‐ and B‐lymphocytes in rheumatic diseases

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