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1.
J Immunol ; 172(1): 392-7, 2004 Jan 01.
Article in English | MEDLINE | ID: mdl-14688347

ABSTRACT

HSV infects skin or mucosal epithelium as well as entering the sensory nerves and ganglia. We have used TCR-transgenic T cells specific for the immunodominant class I-restricted determinant from HSV glycoprotein B (gB) combined with a flank zosteriform model of infection to examine the ability of CD8+ T cells to deal with infection. During the course of zosteriform disease, virus rapidly spreads from the primary inoculation site in the skin to sensory dorsal root ganglia and subsequently reappears in the distal flank. Virus begins to be cleared from all sites about 5 days after infection when gB-specific CD8+ T cells first appear within infected tissues. Although activated gB-specific effectors can partially limit virus egress from the skin, they do so only at the earliest times after infection and are ineffective at halting the progression of zosteriform disease once virus has left the inoculation site. In contrast, these same T cells can completely clear ongoing lytic replication if transferred into infected immunocompromised RAG-1-/- mice. Therefore, we propose that the role of CD8+ T cells during the normal course of disease is to clear replicating virus after infection is well established rather than limit the initial spread of HSV from the primary site of inoculation.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/virology , Ganglia, Spinal/immunology , Herpes Simplex/prevention & control , Herpesvirus 1, Human/immunology , Peripheral Nervous System Diseases/prevention & control , Skin Diseases, Viral/prevention & control , Viral Envelope Proteins/immunology , Administration, Cutaneous , Adoptive Transfer , Animals , CD8-Positive T-Lymphocytes/transplantation , Disease Progression , Epitopes, T-Lymphocyte/immunology , Female , Ganglia, Spinal/pathology , Ganglia, Spinal/virology , Herpes Simplex/immunology , Herpes Simplex/pathology , Herpesvirus 1, Human/growth & development , Hindlimb , Mice , Mice, Inbred C57BL , Mice, Knockout , Mice, Transgenic , Peripheral Nervous System Diseases/immunology , Peripheral Nervous System Diseases/pathology , Receptors, Antigen, T-Cell/genetics , Skin Diseases, Viral/immunology , Skin Diseases, Viral/pathology , Virus Replication/immunology
2.
Eur J Immunol ; 33(6): 1557-67, 2003 Jun.
Article in English | MEDLINE | ID: mdl-12778473

ABSTRACT

We have used a TCR beta-chain transgenic mouse to examine the relationship between the ability of a T cell to bind soluble class I-peptide complexes and its response to antigenic stimulation in vivo. T cells from gBT-I.3beta TCR beta-chain transgenic mice preferentially carried TCR alpha-chains bearing the same Valpha2 V region as found in the parent receptor specific for an immunodominant HSV-1 gB-peptide. Furthermore, CD8(+) T cells from these mice bound K(b)-gB tetrameric complexes with relatively high frequency, and most of these cells contained a Valpha2 TCR alpha-chain. Detailed sequence analysis of the tetramer-binding peripheral T cells showed that this was a heterogenous population expressing TCR with only partial sequence similarity to the parent receptor, which took the form of preferential inclusion of the parental Jalpha16 element. Infection with HSV-1, however, selected a subset of tetramer-positive T cells. This was based on the emergence of a co-dominant Jalpha usage and selection of a restricted CDR3alpha length. Therefore, the ability to bind soluble MHC-peptide complexes does not always correlate with the ability of a T cell to respond to its cognate antigen after in vivo stimulation.


Subject(s)
Antigens, Viral/immunology , Epitopes, T-Lymphocyte/immunology , Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor , Genes, T-Cell Receptor alpha , Genes, T-Cell Receptor beta , H-2 Antigens/immunology , Herpes Simplex/immunology , Immunodominant Epitopes/immunology , Lymphocyte Activation , Peptide Fragments/immunology , Receptors, Antigen, T-Cell, alpha-beta/genetics , Simplexvirus/immunology , T-Lymphocyte Subsets/immunology , Viral Envelope Proteins/immunology , Adoptive Transfer , Animals , Antigens, Viral/metabolism , Biopolymers , Complementarity Determining Regions/genetics , Gene Rearrangement, beta-Chain T-Cell Antigen Receptor , H-2 Antigens/metabolism , Macromolecular Substances , Mice , Mice, Inbred C57BL , Mice, Transgenic , Peptide Fragments/metabolism , Specific Pathogen-Free Organisms , Thymus Gland/immunology , Viral Envelope Proteins/metabolism
3.
Vital Health Stat 10 ; (212): 1-137, 2003 Aug.
Article in English | MEDLINE | ID: mdl-15786610

ABSTRACT

OBJECTIVES: This report presents health statistics from the 1999 National Health Interview Survey (NHIS) for the civilian, noninstitutionalized adult population, classified by sex, age, race and Hispanic origin, poverty status, and region of residence for chronic condition prevalence, health status and limitations in activity, health care access and utilization, health behaviors, and attitudes toward Acquired Immune Deficiency Syndrome (AIDS). Also, health statistics by education, income, health insurance coverage, marital status, and place of residence are presented for health status and limitations in activity, health care access and utilization, health behaviors, and knowledge and attitudes toward AIDS. SOURCE OF DATA: The NHIS is a multistage probability sample survey conducted annually by interviewers of the U.S. Census Bureau for the National Center for Health Statistics, Centers for Disease Control and Prevention, and is representative of the civilian noninstitutionalized U.S. population. Data are collected during face-to-face interviews with adults present at the time of the interview. The self-reported health information for adults in this report was obtained from one randomly-selected adult per family. HIGHLIGHTS: In 1999, 65% of adults 18 years of age or over reported excellent or very good health. However, 17% of adults less than 65 years of age had no health insurance coverage, and 16% of adults did not have a usual place of medical care. Eleven percent of adults had ever been told by a doctor or health professional that they had heart disease and 19% had been told on two or more visits that they had hypertension. Nearly a quarter of adults were current smokers, while 23% were former smokers. Sixty-one percent did not engage in any leisure-time vigorous physical activity, and, based on estimates of body mass index, 35% were overweight and 21% were obese.


Subject(s)
Health Status Indicators , Health Surveys , Vital Statistics , Adolescent , Adult , Aged , Disease/classification , Female , Health Services/statistics & numerical data , Humans , Life Style , Male , Mental Health , Middle Aged , Social Class , United States/epidemiology
4.
J Immunol ; 168(2): 834-8, 2002 Jan 15.
Article in English | MEDLINE | ID: mdl-11777979

ABSTRACT

We have examined the generation of CTL immunity immediately after localized footpad infection with herpes simplex virus 1 (HSV-1) using three coordinated in vivo T cell tracking methodologies. Tetrameric MHC class I containing the immunodominant peptide from HSV-1 glycoprotein B (gB) showed that after infection the proportion of Ag-specific T cells peaked at day 5 within draining popliteal lymph nodes and 2 days later in the spleen. Preferential expression of the activation marker CD25 by tetramer-positive cells in draining popliteal nodes but not spleen suggested that gB-specific T cells were initially activated within the lymph node. In vivo cytotoxicity assays showed that Ag-specific effector cells were present within the draining lymph nodes as early as day 2 after infection, with a further 2-day lag before detection in the spleen. Consistent with the very early arming of effector CTL in the draining lymph node, adoptive transfer of CFSE-labeled gB-specific transgenic T cells showed that they had undergone one to four rounds of cell division by day 2 after infection. In contrast, proliferating T cells were first detected in appreciable numbers in the spleen on day 4, at which time they had undergone extensive cell division. These data demonstrate that HSV-1-specific T cells are rapidly activated and armed within draining lymph nodes shortly after localized HSV-1 infection. This is followed by their dissemination to other compartments such as the spleen, where they further proliferate in an Ag-independent fashion.


Subject(s)
Cell Movement/immunology , Cytotoxicity, Immunologic , Herpes Simplex/immunology , Herpesvirus 1, Human/immunology , Lymph Nodes/immunology , Spleen/immunology , T-Lymphocytes, Cytotoxic/immunology , Animals , Cell Division/immunology , Epitopes, T-Lymphocyte/analysis , Herpes Simplex/pathology , Hindlimb , Histocompatibility Antigens Class I/analysis , Injections, Subcutaneous , Lymph Nodes/pathology , Lymphocyte Activation , Lymphoid Tissue/immunology , Lymphoid Tissue/pathology , Mice , Mice, Inbred C57BL , Mice, Transgenic , Spleen/pathology , Viral Envelope Proteins/immunology
5.
Vital Health Stat 10 ; (205): 1-109, 2002 May.
Article in English | MEDLINE | ID: mdl-15786607

ABSTRACT

This report presents health statistics from the 1997 National Health Interview Survey for the civilian noninstitutionalized adult population, classified by sex, age, race and Hispanic origin, poverty status, region of residence, and where appropriate, education, income, health insurance coverage, marital status, and place of residence. The topics covered are health status and limitations in activity, health care access and utilization, health behaviors and lifestyle, chronic condition prevalence, and knowledge and attitudes toward the Acquired Immunodeficiency Syndrome (AIDS). Source of Data The NHIS is a multistage probability sample survey conducted annually by interviewers of the U.S. Census Bureau for the National Center for Health Statistics, Centers for Disease Control and Prevention, and is representative of the civilian noninstitutionalized U.S. population. Data are collected during face-to-face interviews. Highlights Among adults 18 years of age or over, 12% had ever been told by a doctor or health professional that they had heart disease, 6% had ever been told they had coronary heart disease, and 19% had been told on two visits or more that they had hypertension. Nearly a quarter of adults were current smokers, 23% were former smokers, and 52% had never smoked. Sixty-one percent did not engage in any leisure-time vigorous physical activity, while approximately 24% engaged in such activity three times or more per week. Based on estimates of body mass index, 4% of adults were underweight, 42% were at a healthy weight, 35% were overweight, and 19% were obese.


Subject(s)
Disease/classification , Health Status Indicators , Health Surveys , Adolescent , Adult , Aged , Attitude , Female , Health Services/statistics & numerical data , Health Services Accessibility/statistics & numerical data , Humans , Life Style , Male , Middle Aged , United States/epidemiology
6.
Vital Health Stat 10 ; (209): 1-113, 2002 Dec.
Article in English | MEDLINE | ID: mdl-15790299

ABSTRACT

OBJECTIVES: This report presents health statistics from the 1998 National Health Interview Survey for the civilian noninstitutionalized adult population, classified by sex, age, race and Hispanic origin, poverty status, and region of residence for chronic condition prevalence, health status and limitations in activity, health care access and utilization, health behaviors, and attitudes toward acquired immunodeficiency syndrome (AIDS). Health statistics by education, income, health insurance coverage, marital status, and place of residence are also presented for health status and limitations in activity, health care access and utilization, health behaviors, and knowledge and attitudes toward AIDS. SOURCE OF DATA: The NHIS is a multistage probability sample survey conducted annually by interviewers of the U.S. Census Bureau for the National Center for Health Statistics, Centers for Disease Control and Prevention, and is representative of the civilian noninstitutionalized U.S. population. Data are collected during face-to-face interviews with adults present at the time of the interview. Also, the self-reported health information for adults in this report was obtained from one randomly selected adult per family. HIGHLIGHTS: In 1998, 65% of adults 18 years of age and over reported excellent or very good health. However, 17% of adults less than 65 years of age had no health insurance coverage, and 14% of adults did not have a usual place of medical care. Twelve percent of adults had ever been told by a doctor or health professional that they had heart disease and 19% had been told on two or more visits that they had hypertension. Nearly a quarter of adults were current smokers, and 23% were former smokers. Sixty percent did not engage in any leisure-time vigorous physical activity, and based on estimates of body mass index, 35% were overweight and 20% were obese.


Subject(s)
Health Status , Absenteeism , Activities of Daily Living , Adolescent , Adult , Age Distribution , Aged , Female , Health Behavior , Health Care Surveys , Health Services/standards , Health Services/statistics & numerical data , Health Services Accessibility/standards , Health Surveys , Humans , Male , Middle Aged , Morbidity , Population Surveillance , Prevalence , Racial Groups , Sex Distribution , Socioeconomic Factors , United States/epidemiology
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