scholarly journals Multiple H-2-linked immune response gene control of H-2D- associated T-cell-mediated lympholysis to trinitrophenyl-modified autologous cells: Ir-like genes mapping to the left of I-A and within the I region

1976 ◽  
Vol 144 (6) ◽  
pp. 1701-1706 ◽  
Author(s):  
A Schmitt-Verhulst ◽  
GM Shearer
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Immune Response Gene ◽  
Transplantation Antigen ◽  
Additional Contribution ◽  
Effector Cells ◽  
Congenic Strains ◽  
Chemically Modified ◽  
Cytotoxic Responses ◽  
Ir Genes

One of the more recent associations of the murine H-2 major histocompatibility complex (MHC) with immune function has been the finding that cytotoxic T-effector cells generated by sensitization with viral-infected (1-6), chemically modified (7-9), or weak transplantation antigen-associated (10,11) syngeneic cells can efficiently lyse target cells which express the same viral, chemical, or weak antigenic agent, and which share the H-2K and/or H-2D regions of the MHC with the responding and/or stimulating cells. Furthermore, an additional contribution of a gene(s) within the H-2 complex has been demonstrated which controls immune response potential (Ir genes) in the generation of cytotoxic effector cells to trinitrophenyl (TNP)-modified self components (12,13). In such studies it was found that certain B10 congenic strains generated good cytotoxic responses to both TNP- modified H-2K and H-2D region products, whereas other B10 congenic strains exhibited preferential or exclusive reactivity against TNP-modified H-2K region products. Some of these recombinant strains differing in response potential to TNP- modified H-2D products expressed the same haplotype at the D end, but differed at the K end of H-2. The low responsiveness observed in the B10.A strain to TNP-modified H-2D(d) when compared to B10.D2 and (B10.A x B10.D2)F(1) for the same specificity, suggested a role of dominant Ir genes which map in K, I-A, I-B, I-J, and/or I-E (12, 14). In the present report an attemnpt was made to further map within the MHC the Ir gene(s) controlling cell-mediated lympholysis (CML) to TNP-modified H-2D(d), by using recombinant mouse strains on the A and B10 backgrounds. Irrespective of the genetic background, the s and k haplotypes at the K end generated high and low cytotoxic responses, respectively, to H-2D(d)-TNP. The intermediate responder and low responder status of the A.TL and A.AL strains, respectively, indicated that a gene mapping in the K region of H-2 influences response potential. Furthermore, the differences in the levels of cytotoxicity detected in the A.TH and A.TL strains suggested an additional I region influence. Taken together these findings raise the possibility that multiple genes mapping within different regions of the MHC control the level of T-cell-mediated cytotoxicity to chemically modified autologous cells.

scholarly journals ALLOANTISERUM-INDUCED INHIBITION OF IMMUNE RESPONSE GENE PRODUCT FUNCTION

1974 ◽  
Vol 139 (3) ◽  
pp. 679-695 ◽  
Author(s):  
Ethan M. Shevach ◽  
Ira Green ◽  
William E. Paul
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Lymphocytes ◽  
Cell Surface ◽  
Glutamic Acid ◽  
Gene Product ◽  
Lymphoid Cells ◽  
Immune Response Gene ◽  
Ga Response ◽  
Ir Genes

It has been previously demonstrated that alloantisera can specifically block the activation of T lymphocytes by antigens, the response to which is linked to the presence of histocompatibility (H) types against which the alloantisera are directed. Thus, strain 13 anti-2 serum can inhibit the activation of (2 x 13)F1 T lymphocytes by a DNP derivative of a copolymer of L-glutamic acid and L-lysine (DNP-GL), an antigen the response to which is controlled by a 2-linked Ir gene. It was proposed that alloantisera can inhibit T-lymphocyte antigen recognition through interference with the activity of immune response (Ir) gene products. In order to further study whether the inhibitory antibodies within the alloantisera are directed against H antigens or against the products of the Ir genes, we have examined whether the anti-2 serum can inhibit the function of an Ir gene (the L-glutamic acid and L-alanine [GA] gene), which is normally linked to strain 2 H genes when this gene occurs in an outbred animal lacking strain 2 H genes. In the majority of cases, the anti-2 serum was capable of inhibiting the in vitro proliferative response to GA of T cells derived from animals that were GA+2+, but the serum had little if any effect on the GA response of T cells from GA+2- animals. Furthermore, an antiserum prepared in strain 13 animals against the lymphoid cells of a GA+2- outbred animal was devoid of inhibitory activity on the GA response of cells from a (2 x 13)F1, while an antiserum prepared in strain 13 animals against the lymphoid cells of a GA+2+ outbred animal was capable of specifically inhibiting the response to GA. It thus appears that the inhibition of the GA response by the anti-2 serum is primarily mediated via antibodies directed toward strain 2 H antigens rather than antibodies specific for the product of the GA Ir gene. The mechanism of alloantiserum induced suppression of Ir gene function would then be by steric interference with the Ir gene product on the cell surface, rather than by direct binding to it. This conclusion implies that the products of both the H genes and the Ir genes are physically related on the cell surface. The implications of such a relationship in terms of the fluid-mosaic model of the lymphocyte surface are discussed.

scholarly journals Selective response to H-Y antigen by F1 female mice sensitized to F1 male cells.

1977 ◽  
Vol 146 (2) ◽  
pp. 606-610 ◽  
Author(s):  
R D Gordon ◽  
L E Samelson ◽  
E Simpson
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Target Cells ◽  
Gene Products ◽  
Gene Complex ◽  
Suppressor Genes ◽  
Cytotoxic Responses ◽  
Major Histocompatibility Gene

T-cell mediated cytotoxic responses to H-Y antigen require co-recognition of H-Y and H-2 gene products. F1 mael stimulating cells and target cells express H-Y antigen in association with both parental H-2 haplotypes. However, F1 females primed in vivo and challenged in vitro with F1 male cells lyse male target cells of F1 and only one parental H-2 haplotype. Thus, (CBA X B10)F1 females sensitized to (CBA X B10)F1 male cells lyse (CBA X B10)F1 and CBA but not B10 male target cells, and (BALB/c X B10)F1 females sensitized to (BALB/c X B10)F1 male cells will lyse (BALB/c X B10)F1 and B10 but not BALB/c male target cells. It is suggested that this may represent an effect of immune response or suppressor genes mapping in the major histocompatibility gene complex which regulate responsiveness to H-Y antigen.

Do CD8 effector cells need IL-7R expression to become resting memory cells?

Blood ◽  
2006 ◽  
Vol 108 (6) ◽  
pp. 1949-1956 ◽  
Author(s):  
Eva Buentke ◽  
Anne Mathiot ◽  
Mauro Tolaini ◽  
James Di Santo ◽  
Rose Zamoyska ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Half Life ◽  
Effector T Cells ◽  
Memory Cells ◽  
Effector Cells ◽  
Physiological Conditions ◽  
Transgenic Model

Abstract The role for IL-7R expression in the differentiation of effector T cells into resting memory remains controversial. Here, using a conditional IL-7R transgenic model, we were able to test directly whether CD8 effector T cells require IL-7R expression for their differentiation into resting memory cells. In the absence of IL-7R expression, effector cells transferred into “full” hosts underwent a protracted and unremitting contraction compared with IL-7R–expressing control cells and were unable to develop into long-term resting memory cells. Surprisingly, when the same effector cells were transferred into empty T-cell–deficient hosts, they could generate long-lived fully functional resting memory cells independently of IL-7R expression. Formation of these latter cells was found to be dependent on IL-15, because the same IL-7R–deficient effector cells were rapidly lost from IL-15–deficient hosts, having a half-life of less than 40 hours. Therefore, our data suggest that, under physiological conditions, both IL-7 and IL-15 synergize to promote the formation of memory cells directly by limiting the contraction of effectors that occurs following an immune response and that reexpression of IL-7R is a key checkpoint in the regulation of this process.

scholarly journals ACTIVATION OF T AND B LYMPHOCYTES IN VITRO

1974 ◽  
Vol 140 (6) ◽  
pp. 1717-1722 ◽  
Author(s):  
Dieter Armerding ◽  
David H. Sachs ◽  
David H. Katz
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Immune Responses ◽  
B Lymphocytes ◽  
Critical Role ◽  
Cell Interactions ◽  
Biologically Active ◽  
Immune Response Gene ◽  
Gene Products ◽  
Cell Cell

Observations from our own laboratories, as well as those of others, have demonstrated the critical role of histocompatibility gene products in governing the cell-cell interactions concerned with development and regulation of immune responses in several species (8–12). In mice, the relevant genes concerned have been shown to be located in the K end of the H-2 complex, i.e. in the K and/or I See PDF for Structure regions (13, 14). These discoveries have placed histocompatibility gene products on a more complex level of biologic function than was heretofore generally considered (15). Thus, the hypothesis was made from these observations that genes in the H-2 complex coded for products involved in the development of effective cell-cell interactions in the immune response (8, 9, 15). The recent identification of cell surface macromolecules on lymphocytes and macrophages, that may be distinct from immune response gene products but are likewise coded for by genes in the I region, has provided a group of suitable candidate molecules for such a role (2). In our initial studies on the biological and biochemical characteristics of AEF, we were impressed by the apparent preferential activity of the highly purified AEF preparations on B lymphocytes syngeneic to the activated T-cell population from which the AEF was obtained (1). Since a prediction of the aforementioned hypothesis is, of course, that the active molecules involved in regulatory immunocompetent cell interactions are gene products of the H-2 complex, and, accordingly, should be reactive with antisera directed against components of this complex, we were prompted to perform the appropriate analyses on our preparation of AEF. The experiments presented here demonstrate that the enhancing activity of AEF obtained from T cells of the H-2d haplotype can be specifically removed by immunoadsorbents prepared from antisera reactive with la molecules of the H-2d allele. Identical results were obtained in experiments with both direct and indirect absorption procedures. The possibility that the reaction of AEF with the B10.A anti-B10 (anti-Ia.8) antiserum resulted in release of some components that were in turn toxic to the cultured cells, has been made unlikely in these studies by the use of a direct adsorption method utilizing an immunoadsorbent prepared from thoroughly washed glutaraldehyde-linked antibodies. The results obtained with the (B6A)F1 anti-B10.D2 antiserum deserve some comment. This antiserum contains antibodies directed predominantly against the H-2K region specificity, H-2.31, but may also be reactive with recently determined Iad specificities (5). The capacity of this antiserum to directly absorb approximately 45% of the AEF activity at the lowest concentration of AEF employed (Fig. 1) could be interpreted to indicate the reactivity of AEF with anti-H-2K antibodies. However, the data presented here are also consistent with the interpretation that partial adsorption by the direct immunoadsorbent and lack of adsorption by the indirect method (in which only a high concentration of AEF was incubated with the alloantisera) reflect reactivity of AEF with anti-Iad antibodies present in this antiserum. We conclude, therefore, that the biologically active enhancing moieties of AEF bear Ia determinants and therefore are most probably gene products of the I region of the H-2 gene complex. Recent data from other investigators have shown that an antigen-specific T-cell product could be specifically adsorbed by immunoadsorbents prepared from antisera directed against the K end of H-2 (16). Since the latter antisera may contain antibodies reactive with specificities of both K and I regions, it is possible that the use of selective anti-Ia sera may yield results consistent with those presented here. Taken collectively, these observations indicate that I-region gene products may be intimately involved in the mechanism of cell-cell interactions and responsible for the regulation of immune responses.

scholarly journals Transplantation behavior of A.TH and A.TL T-cell lymphomas in congenic resistant and hybrid strains.

1975 ◽  
Vol 142 (2) ◽  
pp. 536-541 ◽  
Author(s):  
J W Goding ◽  
N L Warner
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Chromosomal Segment ◽  
Immune Response Gene ◽  
Response Gene ◽  
T Cell Lymphomas

Seven spontaneously arising T-cell lymphomas originating in A.TH or A.TL mice, which are congenic for the immune response gene (I) chromosomal segment were described. When transplanted into partner strains which were incompatible at the I region, the tumors were rapidly rejected. Rejection was proposed to be due to the presence of antigens controlled by I-region genes.

scholarly journals Regulation of T Cells in Cancer by Nitric Oxide

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2655
Author(s):  
Inesa Navasardyan ◽  
Benjamin Bonavida
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Suppressor Cells ◽  
T Cell Response ◽  
T Cell Subsets ◽  
Target Cells ◽  
Effector Cells ◽  
Cell Functions

The T cell-mediated immune response is primarily involved in the fight against infectious diseases and cancer and its underlying mechanisms are complex. The anti-tumor T cell response is regulated by various T cell subsets and other cells and tissues in the tumor microenvironment (TME). Various mechanisms are involved in the regulation of these various effector cells. One mechanism is the iNOS/.NO that has been reported to be intimately involved in the regulation and differentiation of the various cells that regulate the anti-tumor CD8 T cells. Both endogenous and exogenous .NO are implicated in this regulation. Importantly, the exposure of T cells to .NO had different effects on the immune response, depending on the .NO concentration and time of exposure. For instance, iNOS in T cells regulates activation-induced cell death and inhibits Treg induction. Effector CD8 T cells exposed to .NO result in the upregulation of death receptors and enhance their anti-tumor cytotoxic activity. .NO-Tregs suppress CD4 Th17 cells and their differentiation. Myeloid-derived suppressor cells (MDSCs) expressing iNOS inhibit T cell functions via .NO and inhibit anti-tumor CD8 T cells. Therefore, both .NO donors and .NO inhibitors are potential therapeutics tailored to specific target cells that regulate the T cell effector anti-tumor response.

scholarly journals The xid gene controls Ia.W39-associated immune response gene function.

1981 ◽  
Vol 153 (5) ◽  
pp. 1113-1123 ◽  
Author(s):  
L J Rosenwasser ◽  
B T Huber
Keyword(s):  
Immune Response ◽  
Gene Function ◽  
Immune Response Gene ◽  
T Cell Proliferation ◽  
Response Gene ◽  
Histocompatibility Complex ◽  
Ia Antigens ◽  
Antigen Presenting ◽  
Ir Genes

Immune response (Ir) genes are encoded for by the I region of the major histocompatibility complex (MHC). A class of serologically defined specificities, Ia antigens, is also encoded for by genes within this region. A new Ia specificity, Ia.W39, has recently been defined. It is private for I-Ab and its expression is controlled by a gene on the X-chromosome. Using different approaches, the role of Ia.W39 in the immune response of H-2b mice to beef insulin was examined in a macrophage-dependent T cell proliferation assay. It was found that beef insulin-related Ir gene function was associated with the expression of Ia.W39 by antigen-presenting macrophages and that control of this Ir gene function was X-linked (xid gene).

scholarly journals Resistance genes to murine leukemia in the I immune response gene region of the H-2 complex.

1977 ◽  
Vol 146 (4) ◽  
pp. 1164-1168 ◽  
Author(s):  
P Lonai ◽  
N Haran-Ghera
Keyword(s):  
Immune Response ◽  
Leukemia Virus ◽  
Genetic Regulation ◽  
Immune Response Gene ◽  
Resistance Locus ◽  
Immune Responsiveness ◽  
Response Gene ◽  
The Right ◽  
Murine Leukemia ◽  
Ir Genes

A resistance locus to leukemogenesis in mice by A-RadLV (a variant of the radiation leukemia virus) is described. This locus, Rrv-1, was mapped to subregions I-A, I-B, and I-J of the H-2 complex. It is suggested that Rrv-1 may be in complementation with a second locus to the right of it, between Rrv-1 and H-2D. This localization and the complementation of the two loci for resistance are characteristics similar to Ir genes, and indicate a possible relationship between the genetic regulation of immune responsiveness and susceptibility to leukemia.

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