Quantitation and Cloning of Cytolytic T Lymphocytes and their Precursors

MacDonald, H. Robson; Cerottini, Jean‐Charles; Ryser, Jean-Etienne; Maryanski, Janet L.; Taswell, Carl; Widmer, Michael B.; Brunner, K. T.

doi:10.1111/j.1600-065x.1980.tb00318.x

Cited by 204 publications

(83 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently it has been demonstrated, at the clonal level, that the sets of alloreactive and H-2-restricted antigen-specific cytolytic and proliferative T cells do overlap (12,15,34,38). In fact, alloantigen and H-2-restricted antigen recognition might not be mediated by functionally different T cell subsets, but might reflect recognition by cross-reactive T cells.…”

Section: Specificity Analysis Ofalloreactive Htlp the Next Set Of Exmentioning

confidence: 99%

T-T cell interactions during in vitro cytotoxic T lymphocyte responses. V. Precursor frequencies and specificity of alloreactive helper T cells.

Krönke¹,

Scheurich²,

Pfizenmaier³

et al. 1982

The Journal of Experimental Medicine

View full text Add to dashboard Cite

The in vitro induction of antigen-specific cytotoxic T lymphocytes (CTL) 1 requires the collaboration between functionally dintinct T cell subpopulations (1-5). Studies at the population level have revealed that upon antigen-specific activation, helper T lymphocytes (HTL) release nonspecific mediators of T help such as interleukin 2 (I1-2), which in turn promote clonal expansion and maturation of antigen-triggered precursors of CTL (CTLp) into cytotoxic effector cells (6-11). Consequently, the efficiency of generating a T cell response depends upon the precursor frequencies of both the regulatory and effector T ceils reactive to the antigen in question.The understanding of the relative roles of functionally distinct T cell subsets during the induction of CTL requires investigations of both the quantitative representation and the specificity repertoire of the respective T cell subset within the responder population. For this type of analysis, however, experimentation at the clonal level rather than at the population level is mandatory. In this regard, the frequency analysis of CTLp and specificity analysis of cloned lines of CTL has provided new information on the expression and development of the repertoire of alloreactive, self-major histocompatibility complex-(MHC) restricted and allo-MHC-restricted antigen-specific sets of . However, information is sparse on the frequency and specificity of precursors of helper T lymphocytes (HTLp) required for differentiation and proliferation of CTLp (16). This communication records our results on limiting dilution analysis to enumerate the precursor frequencies of helper T cells for specific antigen responses in splenic T cells. We present evidence for an absolute requirement of alloreactive Lyt-1 ÷ HTL or their soluble products for the generation of CTL from the pool of Lyt-123 + and Lyt-23 + T cells. Furthermore, we establish the frequency distribution of HTL reactive to different cell surface antigens coded for by the MHC and Mls locus. Finally, we define the antigen specificity of HTL at the clonal level.

show abstract

Section: Specificity Analysis Ofalloreactive Htlp the Next Set Of Exmentioning

confidence: 99%

T-T cell interactions during in vitro cytotoxic T lymphocyte responses. V. Precursor frequencies and specificity of alloreactive helper T cells.

Krönke¹,

Scheurich²,

Pfizenmaier³

et al. 1982

The Journal of Experimental Medicine

View full text Add to dashboard Cite

show abstract

“…Cells recovered from MLTC were washed and restimulated with irradiated MBL-2 and syngeneic feeder cells for a further 7 days in complete medium supplemented with 30 U/ml of IL-2 (EL-4 cell supernatant). CTL clones were established by plating MLTC cells at limiting dilution as described previously (21).…”

Section: Mixed Lymphocyte:tumor Cell Cultures (Mltc)mentioning

confidence: 99%

Transgenic Expression of Ly49A on T Cells Impairs a Specific Antitumor Response

Brawand

Lemonnier

MacDonald

et al. 2000

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

Inhibitory MHC receptors determine the reactivity and specificity of NK cells. These receptors can also regulate T cells by modulating TCR-induced effector functions such as cytotoxicity, cytokine production, and proliferation. Here we have assessed the capacity of mouse T cells expressing the inhibitory MHC class I receptor Ly49A to respond to a well-defined tumor Ag in vivo using Ly49A transgenic mice. We find that the presence of Ly49A on the vast majority of lymphocytes prevents the development of a significant Ag-specific CD8+ T cell response and, consequently, the rejection of the tumor. Despite minor alterations in the TCR repertoire of CD8+ T cells in the transgenic lines, precursors of functional tumor-specific CD8+ T cells exist but could not be activated most likely due to a lack of appropriate CD4+ T cell help. Surprisingly, all of these effects are observed in the absence of a known ligand for the Ly49A receptor as defined by its ability to regulate NK cell function. Indeed, we found that the above effects on T cells may be based on a weak interaction of Ly49A with Kb or Db class I molecules. Thus, our data demonstrate that enforced expression of a Ly49A receptor on conventional T cells prevents a specific immune response in vivo and suggest that the functions of T and NK cells are differentially sensitive to the presence of inhibitory MHC class I receptors.

show abstract

“…pCTL frequencies (f) and correlation coefficients (r 2) of regression analysis for Poisson distributions were calculated from plotting the percentage of noncytolytic cultures in each group of wells against the number of cells originally plated in the wells, as described elsewhere (12). In all experiments, r2 values of all curves were >0 .9 .…”

mentioning

confidence: 99%

Alloantigen persistence in induction and maintenance of transplantation tolerance.

Morecki¹,

Leshem²,

Eid³

et al. 1987

The Journal of Experimental Medicine

View full text Add to dashboard Cite

Infusion of parental bone marrow cells into F1 hybrids conditioned by total lymphoid irradiation (TLI) results in chimeras with a high percentage of donor-type cells, and without clinical signs of graft-vs.-host reaction. In these chimeras, a state of tolerance has been shown to be associated with paucity of cytotoxic T lymphocyte percursors (pCTL) reactive with host-type alloantigens. To determine whether the presence of tolerizing alloantigens is essential for maintenance of unresponsiveness, lymphohematopoietic cells obtained from such tolerant chimeras were transferred into supralethally irradiated recipients of two different genotypes: in one case the adoptive recipients were syngeneic with host-type cells, and in the other they were syngeneic with donor-type cells of the original chimeras, thus providing the chimeric cells with a tolerogen-free environment. After "parking" for 4 d in syngeneic donor-type mice, the transferred cells displayed a marked increase in the frequency of pCTL directed against tolerizing alloantigens, whereas a low pCTL frequency directed against the same H-2 target cells was maintained in allogeneic tolerizing-type adoptive recipients. Multiple injections of adoptive donor-type mice with tolerizing-type cells of the original chimera reestablished a low level of cytotoxic precursors. Cytotoxic activity against unrelated alloantigens was independent of the presence of tolerogen-presenting cells in the adoptively transferred mice. Our experimental model suggests that persistence of cells bearing tolerizing alloantigens is an essential requirement for maintenance of previously established tolerance.

show abstract

Quantitation and Cloning of Cytolytic T Lymphocytes and their Precursors

Cited by 204 publications

References 48 publications

T-T cell interactions during in vitro cytotoxic T lymphocyte responses. V. Precursor frequencies and specificity of alloreactive helper T cells.

T-T cell interactions during in vitro cytotoxic T lymphocyte responses. V. Precursor frequencies and specificity of alloreactive helper T cells.

Transgenic Expression of Ly49A on T Cells Impairs a Specific Antitumor Response

Alloantigen persistence in induction and maintenance of transplantation tolerance.

Contact Info

Product

Resources

About