Alternative pathways of T lymphocyte activation.

Bach, Fritz H.; Alter, Barbara J.

doi:10.1084/jem.148.3.829

Cited by 56 publications

(22 citation statements)

References 11 publications

(14 reference statements)

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“…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

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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).

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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

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“…In Table VI (Table VI, groups [3][4][5]. From both the present and previous studies (7), donor-type accessory cells would not be expected to mediate this CTL response, because they would be unable to activate any Th cells in the chimeric responder population.…”

Section: Role Of Il-2 Secretion By Th Cells In the Generation Of Allomentioning

confidence: 99%

Both L3T4+ and Lyt-2+ helper T cells initiate cytotoxic T lymphocyte responses against allogenic major histocompatibility antigens but not against trinitrophenyl-modified self.

Mizuochi¹,

Golding²,

Rosenberg³

et al. 1985

The Journal of Experimental Medicine

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The initiation of immune responses to nearly all soluble antigens requires the activation by accessory cells of class II-restricted helper T (Th) ~ cells (1, 2). In contrast, the role of Th cells in initiating immune responses to membrane antigens, especially to major histocompatibility complex (MHC)-encoded antigens, remains ill-defined and largely a matter of speculation. Since immune responses against MHC antigens are among the most potent of all immune responses, it is of special interest to identify the cellular interactions by which they are initiated (3). We and others have reported (4-8) that cytotoxic T lymphocyte (CTL) responses against class I alloantigens, like responses to soluble antigens, require a T cell-accessory cell interaction for their initiation. Surprisingly, however, we found (7, 8) that the T cells triggered by accessory cells in class I allospecific CTL responses were of two distinct restriction specificities, in that they could be either class If-restricted or unrestricted.This study was undertaken to document the specificity, function, and Lyt phenotype of the T ceils whose activation by accessory ceils is a necessary early event in the generation of CTL responses against class I MHC antigens. That such T cells were Th cells was documented by synergy experiments in which they provided help for the activation of allospecific precursor CTL (pCTL). We found that there are two distinct subpopulations of Th cells that initiate responses to allogeneic class I MHC antigens: (a) an L3T4+,Lyt-2 -subset specific for class II accessory cell MHC determinants, and (b) an L3T4-,Lyt-2 ÷ subset specific for class I accessory cell MHC determinants. Both L3T4 + and Lyt2 + Th cell subsets mediate their helper function, at least in part, by secreting soluble interleukin 2 (IL-2). Finally, L3T4-,Lyt-2 + Th cells initiate responses against allogeneic class L. H. Glimcher is a fellow of theJ. A. Hartford Foundation.

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“…This concept recently has been challenged by the results of a number of investigators (12)(13)(14)(15), and an alternate view has been put forward. My colleagues and I (14,16,17), and others (12,15), have suggested that the Lyt phenotype is strongly correlated with the class of MHC antigen that is recognized.…”

mentioning

confidence: 99%