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

Abstract

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.

Xenogeneic skin graft rejection is especially dependent on CD4+ T cells.

“…If so, then in the case of xenografts, such IL-2 producing CD8+ cells do not appear to function . In vitro investigation of helper-independent CD8+ cells has found that they do not function in response to class II MHC antigens or in response to self class I MHC antigens when modified as if presenting the peptides of nominal antigens (14) . Thus, the question emerges whether the absence of CD4-independent xenograft rejection indicates that xeno- MHC antigens, unlike allo-MHC antigens, must undergo antigen processing and presentation (perhaps entirely in association with class II antigens) in order to elicit an immune response.…”

Involvement of CD4+Th1 Cells in Systemic Immunity Protective against Primary and Secondary Challenges withTrypanosoma cruzi

“…Our results demonstrating that CD4 ϩ Th1 lymphocytes provide an essential immune function necessary for primary but not memory T. cruzi immunity could be explained by a role for Th1 cells in the optimal induction of protective CTL responses. Other studies of a wide variety of antigenic systems have indicated that CD4 ϩ T lymphocytes can provide important helper functions for the generation of effective CTL (2,5,6,10,12,22,25,37,41,50,51). CD4 ϩ Th1 cells could provide an important helper function for the development of protective humoral immune responses.…”

Helper strategy in tumor immunology: Expansion of helper lymphocytes and utilization of helper lymphokines for experimental and clinical immunotherapy

“…Subsequently, Singer and his colleagues demonstrated that a subset of Lyt-2 + T cells functioned as helper cells in the activation of CTL precursors in conventional class I allospecific CTL responses [68]. The helper activity of some of these cells disguised as killers was further confirmed by their ability to produce IL-2 [75], as shown also by clonal analysis [76].…”

“…Distinct types of tumor antigen may predominantly stimulate one or more types of antitumor T cell subset, but it is also feasible that a given tumor antigen induces both Lyt-2 ÷ and Lyt-2-effector T cells. Moreover, it must be remembered that the Lyt-2 ÷ T cell subset does not simply consist of CTL: some of these cells are responsible for helper T cell activity in response to cell surface antigens, such as class I MHC proteins [68]. In effect, it may be greatly incorrect to assume that activated Lyt-2 ÷ (and even LAK cells) can completely eradicate tumor by direct cytolysis.…”