scholarly journals Graft-vs.-host-associated immune suppression is activated by recognition of allogeneic murine I-A antigens.

1983 ◽  
Vol 157 (3) ◽  
pp. 936-946 ◽  
Author(s):  
G M Shearer ◽  
R B Levy
Keyword(s):  
T Lymphocytes ◽  
T Lymphocyte ◽  
Immune Suppression ◽  
Cytotoxic T Lymphocyte ◽  
Spleen Cells ◽  
F1 Hybrid ◽  
Hybrid Mice

Several combinations of F1 hybrid mice were injected intravenously with parental spleen cells to determine the minimal H-2 differences between F1 and parent that are necessary to induce graft-vs.-host-associated immune suppression (GVH-associated suppression). 7-14 d after injection, the spleens of the F1 mice were tested for cytotoxic T lymphocyte potential by in vitro sensitization against trinitrophenyl-self and H-2 alloantigens. The results indicate that parental T lymphocytes must recognize I-A allogeneic determinants of the F1 recipient in order to induce suppression. Recognition of K or D alone or D with I region products other than I-A did not induce suppression. The recognition of I region without K and/or D and even the I-A difference between C57BL/6 and the B6.Cbm12 mutation resulted in immune suppression that was as potent as that resulting from the recognition of K, D, and I together. The possible significance of this function for I-A antigens is discussed with respect to three clinical examples of immune suppression for which this phenomenon may be relevant.

scholarly journals Mutual recognition of parental and F1 lymphocytes. Selective abrogation of cytotoxic potential of F1 lymphocytes by parental lymphocytes.

1980 ◽  
Vol 151 (1) ◽  
pp. 20-31 ◽  
Author(s):  
G M Shearer ◽  
R P Polisson
Keyword(s):  
T Cell ◽  
Cytotoxic Activity ◽  
T Lymphocyte ◽  
Mutual Recognition ◽  
Spleen Cells ◽  
Cytotoxic Potential ◽  
F1 Hybrid ◽  
Hybrid Mice ◽  
Lymphocyte Populations

Four different combinations of F1 hybrid mice [(C57BL/10 X B10.A)F1, (C57BL/10 X B10.BR)F1, B6D2F1, and AKD2F1] were injected intravenously with spleen cells from parental strains. The T-cell-mediated cytotoxic potential of spleen cells from the injected F1 mice was assessed from 4 to 21 d later by in vitro sensitization with trinitrophenyl-modified parental or syngeneic F1 spleen cells (TNP-self) or with allogeneic spleen cells. The cytotoxic potential of the F1 mice to TNP-self as well as to alloantigens was abolished or severely depressed throughout this period when the respective H-2k,a,d parental spleen cells were injected. In contrast, the cytotoxic potential was unaffected or only marginally reduced when H-2b parental cells were injected. The induction of depressed cytotoxic activity was shown to be a result of a population of parental radiosensitive T lymphocytes. The results should be discussed with respect to (a) the genetic and mechanistic parameters associated with the differential depressive effects of parental cells expressing H-2b vs. H-2k,a,d antigens, and (b) the use of this system for investigating allogeneic receptors on T-lymphocyte populations.

scholarly journals Protection against graft vs. host-associated immunosuppression in F1 mice. I. Activation of F1 regulatory cells by host-specific anti-major histocompatibility complex antibodies.

1981 ◽  
Vol 154 (6) ◽  
pp. 1922-1934 ◽  
Author(s):  
U Hurtenbach ◽  
D H Sachs ◽  
G M Shearer
Keyword(s):  
Major Histocompatibility Complex ◽  
Cytotoxic T Lymphocyte ◽  
Major Histocompatibility ◽  
Spleen Cells ◽  
Cell Surface Antigens ◽  
F1 Hybrid ◽  
Histocompatibility Complex ◽  
Parental Haplotype ◽  
Ctl Responses

Injection of parental spleen cells into unirradiated F1 hybrid mice results in suppression of the potential to generate cytotoxic T lymphocyte (CTL) responses in vitro. In an attempt to protect the F1 mice from immunosuppression, the recipients were injected with antibodies specific for major histocompatibility complex (MHC)-encoded antigens of the F1 mice 24 h before inoculation of the parental spleen cells. 8-14 d later, the generation of CTL responses in vitro against H-2 alloantigens was tested. Alloantiserum directed against either parental haplotype of the F1 strain markedly diminished the suppression of CTL activity. Furthermore, monoclonal antibodies recognizing H-2 or Ia antigens protected the F2 mice from parental spleen cell-induced suppression. Although this study has been limited to reagents that recognize host H-2 determinants, these findings do not necessarily imply that protection against graft vs. host (GvH) can be achieved only with anti-MHC antibodies. However, protection was observed only by antibodies reactive with F1 antigens, and small amounts of the alloantibodies were sufficient to diminish CTL suppression. Adoptive transfer of spleen cells from syngeneic F1 mice treated with anti-h-2a alloantiserum 24 h previously provided protection equal to that of injection of the recipients with alloantibodies. The cells necessary for this effect were shown to be T cells and to be radiosensitive to 2000 rad. This cell population is induced by antisera against F1 cell surface antigens and effectively counteracts GvH-associated immuno-suppression.

scholarly journals Genetic control of cytolytic t-lymphocyte responses. II. The role of the host genotype in parental leads to F1 radiation chimeras in the control of the specificity of cytolytic T-lymphocyte responses to trinitrophenyl-modified syngeneic cells.

1978 ◽  
Vol 148 (2) ◽  
pp. 352-359 ◽  
Author(s):  
P Billings ◽  
S J Burakoff ◽  
M E Dorf ◽  
B Benacerraf
Keyword(s):  
T Lymphocyte ◽  
Mixed Lymphocyte Reaction ◽  
Bone Marrow Cells ◽  
Spleen Cells ◽  
Host Genotype ◽  
F1 Hybrid ◽  
Cytolytic T Lymphocyte ◽  
Lymphocyte Responses

Bone marrow cells from C3H (H-2k) mice, a strain that does not exhibit cross-reactive lysis of trinitrophenyl (TNP)-modified allogeneic targets, were allowed to mature in heavily irradiated (B6 times C3H)F1 (H-2b/k) recipients, an F1 hybrid that does demonstrate cross-reactive lysis. Spleen cells from these chimeric mice were removed after 3-4 mo and by H-2 typing shown to be of C3H origin. These cells were found to be tolerant to B6 alloantigens by mixed lymphocyte reaction and cell-mediated cytotoxicity and, when stimulated in vitro with TNP-modified syngeneic cells, now cross-reactively lysed TNP-modified allogeneic targets. These studies demonstrate that the host environment where T cells differentiate influences the specificity of the primary cytolytic T-lymphocyte (CTL) response to TNP-modified syngeneic antigens.

scholarly journals Protection against Lethal Encephalomyocarditis Virus Infection in the Absence of Serum-Neutralizing Antibodies

1998 ◽  
Vol 72 (10) ◽  
pp. 8052-8060 ◽  
Author(s):  
Zane C. Neal ◽  
Gary A. Splitter
Keyword(s):  
T Lymphocytes ◽  
T Lymphocyte ◽  
Neutralizing Antibodies ◽  
Cytotoxic T Lymphocyte ◽  
Encephalomyocarditis Virus ◽  
Cell Mediated Immunity ◽  
Lethal Challenge ◽  
Activation Markers

ABSTRACT Although the ability of serum-neutralizing antibodies to protect against picornavirus infection is well established, the contribution of cell-mediated immunity to protection is uncertain. Using major histocompatibility complex class II-deficient (RHAβ−/−) mice, which are unable to mediate CD4+ T-lymphocyte-dependent humoral responses, we demonstrated antibody-independent protection against lethal encephalomyocarditis virus (EMCV) infection in the natural host. The majority of RHAβ−/− mice inoculated with 104 PFU of attenuated Mengo virus (vMC24) resolved infection and were resistant to lethal challenge with the highly virulent, serotypically identical cardiovirus, EMCV. Protection in these mice was in the absence of detectable serum-neutralizing antibodies. Depletion of CD8+T lymphocytes prior to lethal EMCV challenge ablated protection in vMC24-immunized RHAβ−/− mice. The CD8+ T-lymphocyte-dependent protection observed in vivo may, in part, be the result of cytotoxic T-lymphocyte (CTL) activity, as CD8+ T splenocytes exhibited in vitro cytolysis of EMCV-infected targets. The existence of virus-specific CD8+T-lymphocyte memory in these mice was demonstrated by increased expression of cell surface activation markers CD25, CD69, CD71, and CTLA-4 following antigen-specific reactivation in vitro. Although recall response in vMC24-immunized RHAβ−/− mice was intact and effectual shortly after immunization, protection abated over time, as only 3 of 10 vMC24-immunized RHAβ−/− mice survived when rechallenged 90 days later. The present study demonstrating CD8+ T-lymphocyte-dependent protection in the absence of serum-neutralizing antibodies, coupled with our previous results indicating that vMC24-specific CD4+ T lymphocytes confer protection against lethal EMCV in the absence of prophylactic antibodies, suggests the existence of nonhumoral protective mechanisms against picornavirus infections.

scholarly journals Genetic control of cytolytic T-lymphocyte responses. I. Ir gene control of the specificity of cytolytic T-lymphocyte responses to trinitrophenyl-modified syngeneic cells.

1978 ◽  
Vol 148 (2) ◽  
pp. 341-350 ◽  
Author(s):  
P Billings ◽  
S J Burakoff ◽  
M E Dorf ◽  
B Benacerraf
Keyword(s):  
T Lymphocyte ◽  
Inbred Mouse ◽  
Cross Reactivity ◽  
Mouse Strains ◽  
Gene Control ◽  
F1 Hybrid ◽  
Cytolytic T Lymphocyte ◽  
Lymphocyte Responses ◽  
Hybrid Mice

The ability of cytotoxic T lymphocytes (CTL) induced in vitro to trinitrophenyl (TNP)-modified syngeneic cells to cross-reactively lyse a TNP allogeneic spleen target varies among inbred mouse strains. The cross-reactive CTL phenotype was found to be histocompatibility 2 (H-2) linked and to be dominant in F1 hybrid mice. All strains investigated demonstrated cross-reactivity except for some strains bearing portions of the H-2k haplotype. The gene(s) controlling this response maps to the K and/or I-A region of the H-2 complex. We have termed the immune response (Ir) gene responsible for controlling the specificity of CTL induced to TNP-modified syngeneic cells Ir-X-TNP.

scholarly journals Primary cell-mediated lympholysis response to a maternally transmitted antigen.

1982 ◽  
Vol 156 (6) ◽  
pp. 1866-1871 ◽  
Author(s):  
R Smith ◽  
D P Huston ◽  
R R Rich
Keyword(s):  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Primary Cultures ◽  
Primary Cell ◽  
Spleen Cells ◽  
F1 Hybrid

Mta-specific cytotoxic T lymphocyte (CTL) can be generated in primary cultures of (NZB X B10.D2)F1 spleen cells with H-2-compatible BALB/c stimulator cells. The CTL lyse reciprocal Mta+ (B10.D2 X NZB)F1 as well as H-2-disparate targets, such as B10, B6, and B6-Tlaa; they do not lyse targets from NZB or any F1 hybrid of an NZB mother. The lysis of 51Cr-labeled B10 targets is completely inhibited by unlabeled targets from Mta+ (B10.D2 X NZB)F1, but not from the reciprocal Mta- F1, thus demonstrating H-2-unrestricted lysis of Mta.

scholarly journals Idiotype-specific T lymphocytes. II. capability of generation of idiotype-specific T lymphocytes is determined by corresponding VH gene.

1983 ◽  
Vol 158 (2) ◽  
pp. 635-640 ◽  
Author(s):  
H Yamamoto ◽  
S Bitoh ◽  
S Fujimoto
Keyword(s):  
T Lymphocytes ◽  
Tumor Cells ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Surgical Removal ◽  
Gene Products ◽  
Network Systems ◽  
Histocompatibility Complex ◽  
Vh Gene

MOPC-104E (M104E) idiotype-specific and major histocompatibility complex-restricted T lymphocyte activities were investigated in BALB/c (Igh-1a) and its Igh-1-congenic strains of mice, such as C.AL-20 (Igh-1d), BAB-14 (Igh-1b), and CB-20 (Igh-1b). Idiotype-specific T lymphocytes could be induced in BALB/c and BAB-14 by immunization of viable M104E tumor cells followed by surgical removal and in vitro restimulation with the homologous tumor cells. On the other hand, C.AL-20 and CB-20 mice did not show the idiotype-recognizing capacity even though they could mount comparable cytotoxic T lymphocyte activities against M104E to BALB/c and BAB-14. The results strongly suggest that the inducibility of M104E cross-reactive idiotypy closely paralleled the producibility of corresponding idiotype-specific T lymphocytes. Genetically defined VH gene products might act as internal images that construct idiotype network systems.

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