Determining quantitative immunophenotypes and evaluating their implications

Quantitative immunophenotypes varied widely among > 100 healthy young males but were maintained at characteristic levels within individuals. The initial results (SPIE Proceedings 4260:226) that examined cell numbers and the quantitative expression of adhesion and lineage-specific molecules, e.g., CD2 and CD14, have now been confirmed and extended to include the quantitative expression of inducible molecules such as HLA-DR and perforin (Pf). Some properties, such as the ratio of T helper (Th) to T cytotoxic/suppressor (Tc/s) cells, are known to be genetically determined. Other properties, e.g., the T:B cell ratio, the amount of CD19 per B cell, etc., behaved similarly and may also be inherited traits. Since some patterns observed in these healthy individuals resembled those found in pathological situations we tested whether the patterns could be associated with the occurrence of disease. The current studies shows that there were associations between quantitative immunophenotypes and the subsequent incidence and severity of disease. For example, individuals with characteristically low levels of HLA-DR or B cells or reduced numbers of Pf+ Tc/s cells had more frequent and/or more severe upper respiratory infections. Quantitative immunophenotypes will be more widely measured if the necessary standards are available and if appropriate procedures are made more accessible.

[1]  D. Fearon,et al.  CD19: lowering the threshold for antigen receptor stimulation of B lymphocytes. , 1992, Science.

[2]  L. Majlessi,et al.  Evidence of alternative or concomitant use of perforin- and Fas-dependent pathways in a T cell-mediated negative regulation of Ig production. , 1999, Journal of immunology.

[3]  E. Reinherz,et al.  A Critical Role for CD2 in Both Thymic Selection Events and Mature T Cell Function1 , 2001, The Journal of Immunology.

[4]  M. Rep,et al.  Phenotypic and Functional Separation of Memory and Effector Human CD8+ T Cells , 1997, The Journal of experimental medicine.

[5]  I. Bernard,et al.  A dominant role for the thymus and MHC genes in determining the peripheral CD4/CD8 T cell ratio in the rat. , 1999, Journal of immunology.

[6]  A. BØyum,et al.  The Effect of Strenuous Exercise, Calorie Deficiency and Sleep Deprivation on White Blood Cells, Plasma Immunoglobulins and Cytokines , 1996, Scandinavian journal of immunology.

[7]  B. Kwon,et al.  Induction of perforin and serine esterases in a murine cytotoxic T lymphocyte clone. , 1990, Journal of immunology.

[8]  J. D. Young,et al.  Isolation and biochemical and functional characterization of perforin 1 from cytolytic T-cell granules. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[9]  K. Bendtzen,et al.  Blood levels of CD11bH+ memory T lymphocytes are selectively upregulated in patients with active rheumatoid arthritis , 1999 .

[10]  B. Passlick,et al.  The novel subset of CD14+/CD16+ blood monocytes is expanded in sepsis patients. , 1993, Blood.

[11]  M. Roth,et al.  Interleukin 2 induces the expression of CD45RO and the memory phenotype by CD45RA+ peripheral blood lymphocytes , 1994, The Journal of experimental medicine.

[12]  K. Bendtzen,et al.  Blood levels of CD11b+ memory T lymphocytes are selectively upregulated in patients with active rheumatoid arthritis. , 1999, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[13]  R. Verardi,et al.  Changes in the populations of lymphoid cells in human peripheral blood following physical exercise. , 1984, Clinical and experimental immunology.

[14]  G. Danieli,et al.  Genetic control of the CD4/CD8 T-cell ratio in humans , 1995, Nature Medicine.

[15]  J. Hansen,et al.  Monoclonal antibody 9.3 and anti‐CD11 antibodies define reciprocal subsets of lymphocytes , 1985, European journal of immunology.

[16]  F. Castelli,et al.  CD11b Expression Identifies CD8+CD28+ T Lymphocytes with Phenotype and Function of Both Naive/Memory and Effector Cells1 , 2001, The Journal of Immunology.

[17]  Y. Shinkai,et al.  Interleukin 2 induction of pore-forming protein gene expression in human peripheral blood CD8+ T cells , 1990, The Journal of experimental medicine.

[18]  J A Steinkamp,et al.  Quantitation of cell concentration using the flow cytometer. , 2005, Cytometry.

[19]  R. Ueda,et al.  Immune function in mice lacking the perforin gene. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[20]  P. Bayer,et al.  Precision and accuracy of monocyte counting. Comparison of two hematology analyzers, the manual differential and flow cytometry. , 1995, American Journal of Clinical Pathology.

[21]  N. Martin,et al.  Genetic and environmental causes of variation in basal levels of blood cells , 1999, Twin Research.

[22]  I. Weissman,et al.  Genetic control of T-Cell subset representation in inbred mice , 2004, Immunogenetics.

[23]  B. Passlick,et al.  Identification and characterization of a novel monocyte subpopulation in human peripheral blood. , 1989, Blood.

[24]  E. Podack,et al.  Cytolytic T cell granules. Isolation, structural, biochemical, and functional characterization , 1984, The Journal of experimental medicine.

[25]  D. Vaux,et al.  Bcl-2 prevents apoptosis induced by perforin and granzyme B, but not that mediated by whole cytotoxic lymphocytes. , 1997, Journal of immunology.

[26]  M. Bachmann,et al.  Cd2 Sets Quantitative Thresholds in T Cell Activation , 1999, The Journal of experimental medicine.

[27]  T. Tedder,et al.  Quantitative Genetic Variation in CD19 Expression Correlates with Autoimmunity1 , 2000, The Journal of Immunology.