Phenotype, specificity, and function of T cell subsets and T cell interactions involved in skin allograft rejection.

Abstract

In the present study we used an adoptive transfer model with athymic nude mice to characterize the T cells involved in initiating and mediating skin allograft rejection. It was found that skin allograft rejection in nude mice required the transfer of immunocompetent T cells and that such reconstitution did not itself stimulate the appearance of T cells derived from the nude host. Reconstitution with isolated populations of Lyt-2+/L3T4- T cells resulted in the rapid rejection of MHC class I-disparate skin allografts, whereas reconstitution with isolated populations of L3T4+/Lyt-2- T cells resulted in the rapid rejection of MHC class II-disparate and minor H-disparate skin allografts. By correlating these rejection responses with the functional capabilities of antigen-specific T cells contained within the reconstituting Lyt-2+ and L3T4+ T cell populations, it was noted that skin allografts were only rejected by mice that, as shown by in vitro assessment, contained both lymphokine-secreting Th cells and lymphokine-responsive Tk cells specific for the alloantigens of the graft. The ability of two such functionally distinct T cell subsets to interact in vivo to reject skin allografts was directly demonstrated in H-Y-specific rejection responses by taking advantage of the fact that H-Y-specific Th cells are L3T4+ while H-Y specific Tk cells are Lyt-2+. Finally, the importance of in vivo interactions between functionally distinct Th/T-inducer cells and T killer (Tk)/T-effector cells in skin allograft rejection was demonstrated by the observation that normal B6 mice retain Qala and Kbm6 skin allografts because of a selective deficiency in antigen-specific Th cells, even though they contain T-effector cells that, when activated, are able to reject such allografts. Thus, the ability to reject skin allografts is neither unique to a specialized subset of T cells with a given Lyt phenotype, nor unique to a specialized subset of helper-independent effector T cells with so-called dual function capability. Rather, skin allograft rejection can be mediated by in vivo collaborations between T-inducer cells and T-effector cells, and the two interacting T cell subsets can express different Lyt phenotypes as well as different antigen specificities.

Role of CD4+ and CD8+ T Cells in Allorecognition: Lessons from Corneal Transplantation

“…Cytolysis of donor cells, resulting from the direct recognition of allogeneic MHC class I molecules by CD8 ϩ T cells, is thought to be the effector mechanism of rejection in different models of transplantation (4,9,10). Here, we determined whether the direct activation of CD8 ϩ T cells was required for corneal graft rejection.…”

“…Initial studies using reconstituted nude mice have supported the view that collaboration between helper and effector functional T cell subsets is required to ensure rejection. Either CD4 ϩ or CD8 ϩ T cells could mediate these functions (4). In several models CD4 ϩ T cells have been shown to be necessary and sufficient for the initiation of allograft rejection (5)(6)(7).…”

“…RBC were lysed for 2 min in Tris-NH 4 Cl solution. Spleen cells were washed twice in AIM-V (Life Technologies, Grand Island, NY) medium containing 0.5% FCS and resuspended at 10 7 cells/ml with 0.5% FCS in AIM-V for further use.…”

Complement Regulates CD4 T-Cell Help to CD8 T Cells Required for Murine Allograft Rejection

“…[1][2][3][4][5] Activation, differentiation, and expansion of naive CD8 ϩ T cells into effector cells after transplantation requires T-cell receptor/class I major histocompatibility complex interactions in conjunction with helper signals provided by CD4 ϩ T cells. 6 The importance of CD4 help is highlighted by findings in mice that CD4-cell depletion or genetic deficiency impairs the priming of donor-reactive CD8 ϩ T cells and markedly prolongs cardiac allograft survival.…”

Altered primary CD8+ T cell response to a modified virus Ankara(MVA)‐vectored vaccine in the absence of CD4+ T cell help

“…Thus, fewer studies have focused on the CD4 + T cell help requirement for the primary CD8 + T cell response. While majority of these suggested no impairment of CD8 + T cell priming in the absence of CD4 + T cell help [6,7,[14][15][16]], a few studies using primarily non-inflammatory stimuli suggested that CD4 + T cell help was absolutely or partially required for the generation a primary CD8 + T cell response [17][18][19][20][21]. Examples of the help-dependent model systems include immunization with peptide-pulsed wild-type DC injected into MHC class II-deficient mice or MHC class II-negative DC injected into normal mice [20], and immunization of CD4 -/-mice with Listeria monocytogenes secreting chicken ovalbumin [21].…”