The synergism of B and T lymphocyte attenuator (BTLA) and cytotoxic T lymphocyte associated antigen-4 (CTLA-4) attenuated acute T-cell mediated rejection and prolonged renal graft survival

The major histocompatibility complex class I-restricted cytotoxic T lymphocyte (CTL) response is important in the clearance of viral infections in humans. After influenza A infection, a peptide from the matrix protein, M58-66, is presented in the context of the MHC allele HLA-A0201 and the resulting CTL response is detectable in most HLA-A0201 subjects. An initial study suggested that M58-66-specific CTL clones show conserved T cell receptor (TCR) alpha and beta gene segments. We have addressed the significance of this observation by determining the expression of V beta 17 during the development of M58-66-specific CTL lines in 21 unrelated HLA-A0201 subjects, and analyzing TCR usage by M58-66-specific CTL clones. TCR V beta 17 was the dominant V beta segment used and CD8 V beta 17 expansion correlated with M58-66-specific lysis. Limiting dilution analysis from five subjects showed the M58-66 CTL precursor frequency to vary between 1/54,000 and less than 1/250,000, and that up to 85% of the matrix peptide (M58-66)-specific CTL used the V beta 17 gene segment. The M58-66 specific CTL response was dependent on previous viral exposure and specific V beta 17 expansion, as it was not found in cord blood, despite a readily expandable V beta 17+ CD8+ T cell subpopulation. Sequence analysis of 38 M58-66-specific V beta 17 transcripts from 13 subjects revealed extensive conservation in the CDR3 region including conservation of an arginine-serine motif. To test the dependence of this CTL response on the V beta 17 gene segment, peripheral blood lymphocytes were depleted of CD8+ TCR V beta 17+ cells, before the generation of M58-66-specific CTL. In most cases such depletion blocked or severely reduced the generation of the M58-66-specific response, and under limiting dilution conditions could abolish M58-66-specific CTL precursors. These studies reveal the dependence of this natural human immune response on a particular TCR gene segment.

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Presence of Low Dose of Fludarabine in Cultures Blocks Regulatory T Cell Expansion and Maintains Tumor-Specific Cytotoxic T Lymphocyte Activity Generated with Peripheral Blood Lymphocytes

Pathobiology ◽

10.1159/000124981 ◽

2008 ◽

Vol 75 (3) ◽

pp. 200-208 ◽

Cited By ~ 15

Author(s):

Upendra Hegde ◽

Arvind Chhabra ◽

Subhasis Chattopadhyay ◽

Raja Das ◽

Swagatam Ray ◽

...

Keyword(s):

T Cell ◽

T Lymphocyte ◽

Regulatory T Cell ◽

Peripheral Blood ◽

Cell Expansion ◽

Low Dose ◽

Cytotoxic T Lymphocyte ◽

Peripheral Blood Lymphocytes ◽

Blood Lymphocytes ◽

Lymphocyte Activity

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Induction of neonatal tolerance to H-2k in B6 mice does not allow the emergence of T cells specific for H-2k plus vaccinia virus.

Journal of Experimental Medicine ◽

10.1084/jem.156.3.810 ◽

1982 ◽

Vol 156 (3) ◽

pp. 810-821 ◽

Cited By ~ 3

Author(s):

D H Schwartz ◽

P C Doherty

Keyword(s):

T Cells ◽

T Cell ◽

Vaccinia Virus ◽

Somatic Mutation ◽

T Lymphocyte ◽

Cytotoxic T Lymphocyte ◽

Spleen Cells ◽

Cell Ontogeny ◽

Stimulation Of ◽

Tolerized Mouse

Thymocytes and spleen cells from C57BL/6 mice (H-2b) neonatally tolerized to H-2k alloantigens do not generate an anti-vaccinia response restricted to H-2Kk when adoptively transferred to appropriate irradiated hosts. This is in sharp contrast to the case for negatively selected C57BL/6 spleen cells acutely depleted of alloreactivity. No evidence for suppression was found in cell mixture experiments. We have shown elsewhere that our neonatally tolerized animals have a centrally induced delection-type tolerance in the absence of obvious suppression.2 We now suggest that in the neonatally tolerized mouse, chronic, central delection of anti-H-2k clones during early T cell ontogeny eliminates the major source of cells able to give rise, via somatic mutation and expansion, to anti-H-2Kk + vaccinia specific cytotoxic T lymphocyte precursors (CTL-P) in the adult. A similar mechanism may operate in the (k + b) leads to b chimera; however, the presence of H-2kxb accessory and presenting cells may permit the eventual generation (via cross-stimulation) of an H-2k-restricted vaccinia-specific repertoire. This would account for our observation of such "aberrant recognition" CTL-P emerging in the spleens of older (k x b) leads to b chimeras.

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