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Biomedical subjects

C Jennings

Publications and source records attributed to C Jennings.

At least 37 records · Page 2Linked to original sources

Function and phenotype of immature CD4+ lymphocytes in healthy infants and early lymphocyte activation in uninfected infants of human immunodeficiency virus-infected mothers.

The function and phenotypes of CD4+ lymphocytes in infants are different than in adults and are modulated by maturational changes and exposure to environmental antigens. Infants of non-human immunodeficiency virus (HIV)-infected mothers and uninfected infants of HIV-infected mothers, 0 to 6 months of age, were examined for CD4+ lymphocyte function by in vitro interleukin-2 (IL-2) production and for CD4+ phenotypes by three-color flow cytometry. A minority of these uninfected infants (28%) had functional responses similar to those of healthy adult women (IL-2 production in response to anti-CD3, alloantigen, and mitogen), while the remainder were capable of responding to alloantigen and mitogen but not to anti-CD3. We did demonstrate reduced phytohemagglutinin-stimulated IL-2 production in uninfected infants born to HIV-seropositive mothers compared to that in infants from seronegative mothers. The proportions of CD3+ CD4+, CD4+ HLA-DR- CD38+, and CD4+ CD45RA+ RO- (naive) lymphocytes were much higher in infants than in adults, and the proportions of CD4+ CD45RA- RO+ (memory) and CD4+ CD25+ (IL-2 receptor-bearing) lymphocytes were lower in infants than in adults. The proportions of activated (CD4+ HLA-DR+ CD38+) and memory (CD4+ CD45RA- RO+) lymphocytes were increased in uninfected infants of HIV-infected mothers compared to infants of uninfected mothers. Therefore, T-helper-cell function is immature in many infants, but the CD4+ lymphocytes of some HIV-exposed, uninfected infants have been stimulated by antigen at an early age.

Adult↗

Recognition of multiple epitopes in the human melanoma antigen gp100 by tumor-infiltrating T lymphocytes associated with in vivo tumor regression.

Four of ten HLA-A2-restricted melanoma specific CTL that were derived from tumor-infiltrating lymphocytes (TIL) and administered to patients recognized the gp100 melanoma Ag and nine of ten recognized the MART-1 Ag. Adoptive transfer of the four gp100-reactive CTL, but not the other TIL, resulted in tumor regression when infused into autologous patients along with IL-2. Tumor regression was thus correlated with the recognition of gp100 by the administered T cells (p = 0.0048). To identify the epitopes recognized by these four gp100-reactive CTL, 169 peptides containing HLA-A2.1 binding motifs were synthesized and screened for their recognition by TIL using cytotoxicity and IFN-gamma release assays. Five gp100 epitopes (two for TIL620, three for TIL660, one for TIL1143, and two for TIL1200) were recognized by CTL derived from different patients. Five of eight HLA-A2 binding melanoma epitopes (five gp100, one MART-1/Melan-A, two tyrosinase) had intermediate binding affinity to HLA-A2.1. These gp100 epitopes may be responsible for mediating tumor rejection in vivo and thus may be useful for the development of immunotherapies for patients with melanoma.

Amino Acid Sequence↗

Evidence of a selective depletion of a CD16+ CD56+ CD8+ natural killer cell subset during HIV infection.

Three-color flow cytometric analysis of CD16+ natural killer (NK) cells was assessed in HIV seropositive patients and healthy heterosexual controls. A selective depletion of lymphocytes with the CD16+ NK phenotype was found among the HIV+ infected patients. When the CD16 lymphocyte subset was further evaluated by three-color flow cytometry, cells bearing both the CD8 and CD56 antigens were significantly decreased. Analysis of activation antigens revealed a large proportion of CD16+ NK cells from HIV+ patients expressed HLA-DR, but this did not correlate with CD25 (IL-2 receptor) expression. The overall loss of the CD8 and CD56 antigens among the NK population with an increase in activation status may be due to differential loss of the NK cell subsets or, alternatively, to the loss of immunoregulatory cytokines, which have been shown to be important in maintaining NK activity. Whether these changes in the NK compartment may influence the outcome of individuals with HIV disease still remains an open question but is an important issue when performing phenotypic analysis of HIV+ subjects.

CD4 Lymphocyte Count↗

Genome organisation in the murine sperm nucleus.

The organisation of DNA sequences in the murine sperm nucleus was studied using in situ hybridisation of biotinylated DNA probes. The efficiency of this reaction was assessed using a dispersed repetitive DNA probe. Telomeric DNA was distributed around the nucleus. Centromeric and ribosomal DNA sequences occupied restricted domains in the sperm nucleus. DNA sequences for a transgene and a cluster of homeogenes occupied different, and rather less defined, domains. Together these results imply that both repetitive and protein-coding sequences are arranged in the nucleus in an ordered fashion.

Animals↗

CD4+ lymphocytes in perinatal human immunodeficiency virus (HIV) infection: evidence for pregnancy-induced immune depression in uninfected and HIV-infected women.

Immune function changes during pregnancy and human immunodeficiency virus (HIV) infection. T helper function and phenotypes in HIV-infected and -uninfected pregnant and postpartum women and nonpregnant uninfected control women were studied. T helper function was assessed by interleukin-2 (IL-2) production in vitro and three-color flow cytometry. All uninfected nonpregnant subjects, 74% of uninfected pregnant subjects, and only 54% of HIV-infected pregnant subjects responded to all stimuli. All uninfected subjects 2-6 months postpartum had normal function versus 27% of infected subjects (trend P < .001). Uninfected pregnant subjects had reduced levels of CD4+CD45RA-RO+ (memory) and elevated levels of CD4+CD45RA+RO- (naive) lymphocytes. Infected pregnant subjects had elevated levels of memory, reduced levels of naive, and increased levels of CD4+HLA-DR+CD38+ (activated) lymphocytes. Increased CD4+DR+CD38+ cells correlated best with poor IL-2 function, HIV infection, and being postpartum (R2 = .79). Thus, T helper function and phenotypes are altered in pregnancy and return to baseline postpartum in uninfected but not HIV-infected women.

ADP-ribosyl Cyclase↗

Personality inferences drawn about abusive mothers.

This study investigated the personality inferences people draw about abusive mothers by having 287 subjects view videotapes of four female targets engaged in social discourse with other adults. Some subjects were primed beforehand to believe that the female targets had physically abused or neglected their child and other subjects viewed the tapes without being primed. Afterward, all subjects rated the targets' personalities using 17 bipolar trait scales and estimating the likelihood of six social behaviors. Analyses compared the ratings of the two types of abuse groups (physical abuse and neglect) with each other and with the unprimed control group. Analysis showed that ratings of one or both of the abuse groups differed from those of the control group on 10 of the 17 trait dimensions and four of six social behaviors. Implications are drawn about the social forces experienced by abusive mothers and the possible role of such forces in therapeutic change.

Adult↗

Identification of MART-1-specific T-cell receptors: T cells utilizing distinct T-cell receptor variable and joining regions recognize the same tumor epitope.

Tumor-specific cytotoxic T lymphocytes (CTLs) can mediate tumor regression in patients with metastatic melanoma and play a central role in the immune response to cancer. The recent identification of shared melanoma antigens has raised the possibility of a limited melanoma-specific T-cell receptor (TCR) repertoire, but subsequent studies have been controversial and difficult to interpret without knowing which tumor-associated antigens (TAAs) are being recognized by specific TCRs. However, the recent cloning of several melanoma TAAs now allows for the identification of the specifically recognized TAA and its epitope. We evaluated the TCR of two clonal CD8+ CTL lines, A42 and 1E2, from two HLA-A2+ patients with metastatic melanoma. Both CTL lines were MART-1 specific, and both demonstrate reactivity to the same epitope when presented in an HLA-A2.1 context. The TCR genes of the two clones were sequenced. All of the productively rearranged A42 TCR beta chain genes were V beta 7/D beta 2.1/J beta 2.7/C beta 2; the TCR alpha chain genes were V alpha 21/J alpha 42/C alpha. The 1E2 TCR beta chain genes were V beta 3/D beta 1.1/J beta 1.1/C beta 1, and TCR alpha chains were V alpha 25/J alpha 54/C alpha. This study is the first report of TCR sequences specific for a melanoma epitope. These TCR clones may be useful for the development of more effective immunotherapies and in studies of the mechanism of T-cell recognition of tumor antigen. They also provide direct evidence that the immune system can provide more than one TCR capable of recognizing a TAA epitope.

Antigens, Neoplasm↗