Cooperation between subclasses of T lymphocytes in the <i>in vitro</i> generation of cytotoxicity against a mutant H‐2K difference An analysis with anti‐Lyt antisera

Melief, C. J. M.; Meulen, Marian Y. van der; Christiaans, Bernard J.; Greeve, Paul de

doi:10.1002/eji.1830090103

Cited by 27 publications

(12 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1, B6 anti-bml) with NSC as APC confirms earlier studies [lo, 131 in which the Kbml alloantigen was a potent direct stimulator of the CDX' T cell subset. In addition, the previous finding that this T, response is augmented by CD4' cells [25] is also confirmed. However, bml DC are even more potent stimulators of the CD8' T cell subset because B6 responder cell populations devoid of CD4' Th cells showed an equally strong anti-Kbm' T, response as the untreated population ( Fig.…”

Section: Discussionsupporting

confidence: 62%

Stimulation with dendritic cells decreases or obviates the CD4+ helper cell requirement in cytotoxic T lymphocyte responses

1988

View full text Add to dashboard Cite

We investigated the need for CD4+ helper T (Th) cells in the induction of murine cytotoxic T lymphocyte (Tc) responses across minor or major histocompatibility (MHC) antigenic differences with either normal spleen cells (NSC) or purified dendritic cells (DC) as antigen-presenting cells (APC). Generation of a secondary in vitro class II MHC-specific Tc response was totally CD4+ Th cell-dependent with both types of APC. Likewise, male antigen (H-Y)-primed class II mutant bm12 T cells, which do not respond to H-Y presented on NSC, do respond to H-Y presented on DC in a completely CD4+ Th cell-dependent fashion. All other Tc responses, including primary anti-class I MHC, primary anti-class I + II MHC plus anti-minor H, and secondary C57BL/6 (B6) anti-H-Y, although not completely CD4+ Th cell dependent, were greatly augmented in the presence of CD4+ Th cells, but only with NSC as APC. In contrast, with DC as APC these responses were entirely or largely CD4+ Th cell independent. Similarly, H-Y primed class I MHC mutant bm14 T cells, which do not respond to H-Y presented on NSC, do respond to H-Y presented on DC in a completely CD4+ Th cell-independent fashion. The combined results indicate that DC can directly present class I MHC alloantigen or class I MHC plus nominal antigen (e.g. minor H) to CD8+ cells and generate a Tc response by these cells without the requirement for CD4+ Th cells.

show abstract

Section: Discussionsupporting

confidence: 62%

Stimulation with dendritic cells decreases or obviates the CD4+ helper cell requirement in cytotoxic T lymphocyte responses

1988

View full text Add to dashboard Cite

show abstract

“…In these combinations, the responder and [12,131 have shown that in such combinations, both precursor and effector cells are Lyt-1,2 when generated from the B6-Ly-1" (Lyt-1.1, Lyt-2.2) strain. In contrast, Melief et al [14] have reported that the response of B6 (Lyt-1.2, Lyt-2.2) cells to H-2K mutants involves cooperation between Lyt-1 and Lyt-2 cells, the cytotoxic effectors themselves being Lyt-2. To clarify this point, we have in these experiments used monoclonal rat anti-Lyt antibodies, which recognize nonpolymorphic framework determinants on Lyt antigens [15] and thus permit a direct comparison of the Lyt phenotypes of responder cells carrying different Lyt alleles.…”

Section: Introductionmentioning

confidence: 83%

Terminal differentiation of T cells specific for mutant H‐2K antigens. Conversion of Lyt‐1,2 cells into Lyt‐2 but not Lyt‐1 cells, in vitro

1981

View full text Add to dashboard Cite

The Lyt phenotype of T cells at different stages of response to mutant H-2K antigens was determined by immunofluorescence using monoclonal rat anti-Lyt antibodies. Previous observations indicated a differential expression of the two allelic forms of Lyt-1 antigen on these cells. Since the rat antibodies recognize nonpolymorphic framework determinants of Lyt antigens, in our approach the expression of both Lyt-1 alleles was analyzed with the same antibody. It was found that cells reacting to three different H-2K mutants have the Lyt-1,2 phenotype, regardless of the Lyt-1 allele carried by the responder strain. The Lyt phenotype of responder cells remained unchanged after priming in vivo. However, cells recovered from cultures after secondary stimulation in vitro were mainly Lyt-2, with few Lyt-1,2 and virtually no Lyt-1 cells present. This change of Lyt phenotype ran in parallel with the loss of proliferative capacity to the priming antigen, but cytolytic activity of the cells remained unimpaired. Long-term proliferation of T cells induced against mutant H-2K antigens could only be maintained in the presence of a T cell growth factor. Cultures with growth factor contained almost exclusively Lyt-2 cells and exerted strong cytolytic activity. These results demonstrate that the Lyt differentiation pathway of anti-mutant T cells is from Lyt-1,2 to Lyt-2. Furthermore, the data suggest that no helper cells are induced in response to mutant H-2K antigens. A model which incorporates these findings into current concepts of T cell differentiation is discussed.

show abstract

“…These experiments and others involving responses to foreign H-2 antigens (3) have been interpreted as evidence for an intrinsic I region specificity of helper T cells in CTL responses, although literally they show only that among alloreactive T cells there is a preponderance of I region-specific rather than K, D region-specific cells that produce augmenting signals for CTL. Allospecific CTL responses may not require the participation of T cells with specificity for I region determinants because they can be raised against cells that are allogeneic only at the D or K region as well as against cells expressing mutant K antigens (37)(38)(39).…”

Section: Discussionmentioning

confidence: 99%

Helper T cells for cytotoxic T lymphocytes need not be I region restricted

Raulet¹,

Bevan²

1982

The Journal of Experimental Medicine

View full text Add to dashboard Cite

The development of procedures for the physical or functional separation of B cells and helper T cells permitted extensive studies to be performed that have elucidated the nature of cell-cell interactions that occur during the antibody response. Current models of B cell activation state that antigen-specific helper T cells are activated by recognition of antigen in the context of H-2 I region-encoded determinants on specialized antigen-presenting cells (APC) 1 and then deliver inducing signals to antigen-activated B cells via recognition of antigen plus I region determinants on the B Cell.In contrast, studies of cellular interactions in the cytotoxic T lymphocyte (CTL) response have been hampered by the inability to cleanly separate CTL precursors from their helper T cells (see Discussion). Nonetheless, on the basis of mostly indirect results from a variety of experimental approaches, the most prevalent model of CTL activation is one that closely parallels models of B cell activation, i.e., that I regionrestricted helper T cells activated by interaction with antigen in the context of I region determinants deliver inducing signals to antigen-activated precursor CTL (1-5). In some models, the helper T cell interacts with CTL precursors via the restricted recognition of I region determinants expressed by the CTL precursor (1, 2). Experiments interpreted as supporting the role of I region-recognition events during the process of CTL induction include (a) studies demonstrating the augmentation of CTL responses to foreign H-2K and D antigens by I region-reactive T cells (5, 6), (b) studies of CTL responses to viral (2) or non-H-2 cell surface antigens (7) or hapten (8), demonstrating an influence of I region genes expressed by cells of the thymus on the response phenotype of T cells that mature therein, (c) a study demonstrating the apparent depletion, by in vivo negative selection procedures, of I region-restricted helper cells required for an in vitro secondary CTL response specific for minor histocompatibility antigens (9), and (d) the finding that Ia + non-T accessory cells are required for in vitro CTL responses (4, 10, 1 1). In addition, studies of the Ir gene defect ofnonresponder strains in the CTL response of female mice to the male antigen, H-Y, have been interpreted in terms of I region-restricted helper T cells (1,7,(12)(13)(14)(15).

show abstract

Cooperation between subclasses of T lymphocytes in the in vitro generation of cytotoxicity against a mutant H‐2K difference An analysis with anti‐Lyt antisera

Cited by 27 publications

References 35 publications

Stimulation with dendritic cells decreases or obviates the CD4+ helper cell requirement in cytotoxic T lymphocyte responses

Stimulation with dendritic cells decreases or obviates the CD4+ helper cell requirement in cytotoxic T lymphocyte responses

Terminal differentiation of T cells specific for mutant H‐2K antigens. Conversion of Lyt‐1,2 cells into Lyt‐2 but not Lyt‐1 cells, in vitro

Helper T cells for cytotoxic T lymphocytes need not be I region restricted

Contact Info

Product

Resources

About